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  • pharmacokinetics  (417)
  • Wheat  (108)
  • Springer  (525)
  • American Geophysical Union (AGU)
  • Annual Reviews
  • 1980-1984  (525)
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  • Springer  (525)
  • American Geophysical Union (AGU)
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  • 1
    Digitale Medien
    Digitale Medien
    A note on the rôle of generalized inverse Gaussian distributions of circulatory transit times in pharmacokinetics (1984)
    Springer
    Journal of mathematical biology 20 (1984), S. 95-102 
    Details
    ISSN: 1432-1416
    Schlagwort(e): pharmacokinetics ; generalized inverse Gaussian distribution ; recirculatory model ; renewal theory
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Mathematik
    Notizen: Abstract Based on a stochastic pharmacokinetical model (which mirrors topological properties of the circulatory system) it is shown by reinterpreting results of Wise (1974) that if the transit times of circulating drug molecules have a generalized inverse Gaussian distribution the corresponding residence times are gamma distributed. The condition that the probability of elimination of a drug molecule in a single circulatory passage is sufficiently small appears to be valid for most drugs. Thus theoretical evidence is given for fitting blood concentration-time curves following bolus injection of a single dose by power functions of time.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00275864
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  • 2
    Digitale Medien
    Digitale Medien
    Increasing grain protein content of hard red winter wheat (Triticum aestivum L.) by mutation breeding (1983)
    Springer
    Theoretical and applied genetics 65 (1983), S. 41-46 
    Details
    ISSN: 1432-2242
    Schlagwort(e): Triticum aestivum ; Wheat ; Protein ; Mutation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Poor adaptability or functional quality of much germplasm used for breeding high-protein hard red winter wheats prompted mutagenesis as an alternative means of increasing grain protein content. Four hard red winter wheat genotypes — KS644 (‘Triumph// Concho/Triumph’), ‘Kaw’, ‘Parker’, and ‘Shawnee’ — were treated with 0.40 M ethyl methanesulfonate (EMS). Advanced lines (M8-M10) were selected that had a 3-year mean grain protein advantage of 0.7% to 2.0% over controls. Increased grain protein content was generally associated with decreased grain yield and kernel weight, but some high-protein mutant lines had yields or kernel weights similar to those of original genotypes. Changes in height and lodging induced by EMS were generally favorable, most mutants being shorter and lodging less than controls, but blooming date was generally delayed, a deleterious change. One line also changed from resistant to segregating for wheat soil-borne mosaic virus. Mutant lines might be utilized in cross-breeding programs, particularly if negative pleiotropic effects and linkages are absent.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00276260
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  • 3
    Digitale Medien
    Digitale Medien
    Clinical pharmacokinetics and oral bioavailability of ketobemidone (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 45-50 
    Details
    ISSN: 1432-1041
    Schlagwort(e): ketobemidone ; narcotic analgesic ; N,N-dimethyl-3,3-diphenyl-1-methylallylamine chloride ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The basic pharmacokinetics and oral bioavailability of ketobemidone have been studied in 6 patients after surgery. Plasma concentrations were first determined following intravenous administration of Ketogin® 2 ml, containing ketobemidone chloride 10 mg and the spasmolytic N,N-dimethyl-3,3-diphenyl-1-methylallylamine chloride 50 mg, and then, on the second postoperative day, following oral administration of 2 tablets of Ketogin®, each containing ketobemidone chloride 5 mg and the spasmolytic agent 25 mg. The average oral bioavailability of ketobemidone was 34%±16% (SD, n=6). The mean plasma half-life of elimination (t1/2β) was about the same following oral (2.45±0.73 h; SD, n=5) as after intravenous administration (2.25±0.35 h; SD, n=6). The low oral bioavailability and rapid elimination of ketobemidone demonstrated in this study suggest that the usual dosage recommendation for oral Ketogin® (ketobemidone 5–10 mg every 6–7 h) in patients with severe pain is too low.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561676
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  • 4
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of sodium valproate in epileptic patients: Prediction of maintenance dosage by single-dose study (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 71-77 
    Details
    ISSN: 1432-1041
    Schlagwort(e): sodium valproate ; epileptic patients ; pharmacokinetics ; plasma concentration ; prediction ; maintenance dosage
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Pharmacokinetic analysis of the plasma valproic acid concentration-time course, following a single oral dose (600 mg) of sodium valproate, was performed in 20 epileptic patients as an aid to the prediction of a proper chronic dosage regimen. A simple one-compartment model was found inadequate to describe the drug concentration-time course in 15 of the 20 patients studied. The average elimination (β phase) half-life of 9 h was shorter than that previously reported in healthy subjects. The latter observation and the wide variation in plasma valproic acid clearance observed between patients (0.09–0.53 ml/kg/min) may have been related to its altered disposition by concomitant anticonvulsant therapy. Sodium valproate maintenance therapy, determined by single-dose pharmacokinetic prediction of steady-state plasma valproic acid levels, did not require dosage adjustment because of unwanted effects. However, the occurrence of drug-related adverse events led to dosage reduction in 4 of 9 patients whose chronic therapy was not pharmacokinetically predicted. Moreover, the pharmacokinetic variability demonstrated for sodium valproate by patients on multiple therapy, whose chronic sodium valproate therapy was pharmacokinetically predicted, indicates the value of monitoring plasma valproic acid levels for the regulation of anticonvulsant therapy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561679
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  • 5
    Digitale Medien
    Digitale Medien
    Metabolic and haemodynamic effects and pharmacokinetics of a new selective beta1-adrenoceptor agonist, prenalterol, in man (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 81-86 
    Details
    ISSN: 1432-1041
    Schlagwort(e): prenalterol ; beta1-adrenoceptor agonist ; metabolic effects ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The metabolic and haemodynamic effects of three intravenous doses (0.5, 1.0 and 4.0 mg) of prenalterol, a selective β1-adrenoceptor agonist, were studied in 10 healthy male subjects. Plasma levels of prenalterol during the experiments were related to the haemodynamic effects. Prenalterol induced a dose-dependent increase in systolic blood pressure and heart rate. The maximal effects amounted to about 30 mm Hg and 15 beats/min, respectively, after the highest dose (4.0 mg). The diastolic blood pressure fell by a maximum of about 15 mm Hg. The effect of prenalterol on systolic blood pressure and heart rate persisted for about 3 h after the end of the last infusion, whereas that on diastolic blood pressure only lasted for 60 min. Compared with placebo, there was a moderate increase in plasma FFA and glycerol. A small rise in insulin level was also recorded, but no significant change was seen in other metabolic variables — triglycerides, glucose, lactate, pyruvate. Serum potassium tended to decrease and serum sodium was unchanged. The initial distribution of prenalterol was rapid (half-life 7 min) and the overall elimination rate corresponded to a plasma half-life of 2 h. A linear relationship was found between the plasma level of prenalterol and its effects on systolic blood pressure and heart rate.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562614
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  • 6
    Digitale Medien
    Digitale Medien
    Pharmacokinetic and clinical observations on prolonged administration of flunitrazepam (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 189-196 
    Details
    ISSN: 1432-1041
    Schlagwort(e): flunitrazepam ; prolonged administration ; pharmacokinetics ; clinical observations ; sleep parameters
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Eight patients were given flunitrazepam 2 mg orally, once daily for 28 consecutive days. The time-course of the plasma concentration of unchanged flunitrazepam and its principal metabolites were studied in detail after the first and last doses. Additional blood samples were collected immediately before administration of the tablet on days 4, 7, 11, 14, 18, 21 and 25. Clinically there were no changes during the trial period in the onset of sleep, duration of sleep, depth of sleep measured as number of spontaneous awakenings, or in the patients' condition on awakening. The time-course of the plasma concentration of flunitrazepam could be described by a three-compartment model, assuming that the rate constants remained unchanged during treatment. Maximal plasma concentrations of unchanged flunitrazepam, found two hours after intake, reached 10–15 ng/ml after the first and 15–20 ng/ml after the last dose. The β-half-life was found to be between 20 and 36 h.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561899
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  • 7
    Digitale Medien
    Digitale Medien
    Comparative bioavailability of disopyramide after multiple dosing with standard capsules and controlled-release tablets (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 209-213 
    Details
    ISSN: 1432-1041
    Schlagwort(e): disopyramide ; bioavailability ; controlled-release tablets ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma concentrations and bioavailability of disopyramide following repeated administration of standard capsules and controlled-release tablets have been compared. Ten patients were randomized into two groups; Group I received disopyramide capsules 150 mg every 6 h for five days and subsequently disopyramide controlled-release tablets 300 mg every 12 h for further five days. Group II received the same preparations in the reverse order. There was a more rapid rise in disopyramide concentration after the capsules: the maximum of 10.7±0.6 µmol/l (mean ± SEM) was reached within 1.8±0.4 h as compared to 10.6±0.4 µmol/l within 4.0±0.3 h after the controlled-release tablets. No significant difference in the fluctuations in individual plasma concentrations during each dose interval at steady state were observed after ordinary capsules compared to controlled-release tablets. The extent of bioavailability was the same. Eight patients reported some side-effects during the capsule period and nine during the controlled-release tablet period.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561902
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  • 8
    Digitale Medien
    Digitale Medien
    Systemic availability of orally administered L-dopa in the elderly Parkinsonian patient (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 215-221 
    Details
    ISSN: 1432-1041
    Schlagwort(e): L-dopa ; elderly ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Previous studies have suggested that the absorption of L-dopa in the elderly Parkinsonian patient might be unusually efficient. In the present investigation, the systemic availability of L-dopa was examined in 5 elderly Parkinsonian patients (mean age=77 years) and 6 young, healthy volunteers (mean age=26 years) following a single oral 300 mg dose of L-dopa. Quantitation of plasma levels of intact L-dopa was effected by ion-exchange column chromatography and spectrofluorimetry. The L-dopa plasma concentration-time profiles obtained confirmed the considerable intersubject variability in the absorption of L-dopa previously reported in the literature. Maximum plasma concentrations of L-dopa generally occurred within 60 min of administration of the dose. The existence of more than one plasma peak of L-dopa concentration was displayed in 45% of the subjects studied. This characteristic was not confined exclusively to either subject group. There was a significantly larger (P〈0.02) area under the plasma L-dopa concentration-time curve (AUC o ∞ ) in the elderly Parkinsonian patients (mean=234.69 µg · min/ml; SD=84.70) compared to the young, healthy volunteers (mean=82.33 µg · min/ml; SD=31.00). A significant (P〈0.01) correlation existed between AUC o ∞ and age (r=0.7970; n=11) among the subjects studied. The apparent elimination phase plasma half-life of L-dopa in the elderly Parkinsonian patients (mean=66.0 min; SD=11.1) was not significantly different to that observed in the young, healthy volunteers (mean=74.0 min; SD=18.1). These results suggest that there may be an age-related alteration to the disposition of orally administered L-dopa in the elderly Parkinsonian patient.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561903
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  • 9
    Digitale Medien
    Digitale Medien
    Altered prazosin pharmacokinetics in congestive heart failure (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 425-428 
    Details
    ISSN: 1432-1041
    Schlagwort(e): prazosin ; congestive heart failure ; pharmacokinetics ; oral dose ; comparison with healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of prazosin (Minipress®) were studied in nine patients with NYHA Class 3 or 4 congestive heart failure and in five healthy controls. After a single 5 mg oral dose, plasma concentrations of prazosin, as reflected in the area under the plasma concentration-time curve (AUC) and prazosin plasma half-life, were approximately double in the patients in comparison to the control group. Reduction in hepatic blood flow, altered gastrointestinal absorption of the drug or diminished intrinsic hepatic metabolic activity in the patient group may have contributed to the observed changes in prazosin disposition. The finding of higher prazosin plasma concentrations in patients with refractory heart failure demonstrates the need for close monitoring of these individuals following administration of the drug in the treatment of chronic congestive heart failure.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00570159
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  • 10
    Digitale Medien
    Digitale Medien
    Placental transfer of pethidine and norpethidine and their pharmacokinetics in the newborn (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 25-30 
    Details
    ISSN: 1432-1041
    Schlagwort(e): pethidine ; norpethidine ; placental transfer ; pharmacokinetics ; newborns
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The literature data available on pethidine and norpethidine kinetics in women in labour and in their newborns is reviewed and compared with recent personal observations. In pregnant women the apparent blood half-life of pethidine is not different from that in healthy controls, however, apparent volume of distribution and total body clearance are reduced. Norpethidine blood levels are measurable after 10–20 min and tend to increase with time. The amount of drug transferred to the foetus is clearly linked to the dose administered to the mother, the dosing-delivery interval and to the metabolic capability of the mother. An equilibrium between maternal and umbilical venous blood is reached 2–3 h after dosing for pethidine and later for norpethidine. In the neonate, the apparent pethidine half-life is 2 to 7 times longer than in adults with values ranging from 7 to 32 h. Norpethidine is actively formed in the newborn with peak blood levels at 12–36 h and an apparent blood half-life of 20–36 h. At the doses usually recommended blood concentrations at birth are frequently higher than those required for analgesia and close to or within toxic ranges. An effort toward a more individualized dosage as well as toward a better understanding of the possible role of norpethidine with regard to adverse effects is needed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561475
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  • 11
    Digitale Medien
    Digitale Medien
    Disposition and pharmacodynamics of diuretics and antihypertensive agents in renal disease (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 109-116 
    Details
    ISSN: 1432-1041
    Schlagwort(e): diuretics ; antihypertensive agents ; renal disease ; dispositon ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacodynamic actions and disposition of diuretic and antihypertensive agents may be significantly modified in subjects with renal disease. Most studies on this question have dealt with alterations in the elimination kinetics of these drugs and, while they generate descriptive data, minimal insight about changes in dose-response relationships or mechanisms of drug action are provided by such investigations. Several basic principles which may serve as useful guidelines in determining how renal failure will influence the response to drugs have been considered. They include the following: degree of renal malfunction, intrinsic toxicity of the drug, alternative pathways for drug metabolism and elimination, elimination pharmacokinetics and dose-response characteristics. Several classes of diuretic agents (thiazides, furosemide) and antihypertensive drugs (hydralazine, methyldopa, propranolol, prazosin, and clonidine) have been used as models to define how basic knowledge of renal and non-renal pathways for elimination of drugs and their pharmacodynamic actions may assist in establishing rational therapeutic regimens for these agents in patients with renal failure.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561487
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  • 12
    Digitale Medien
    Digitale Medien
    Influence of cimetidine on the pharmacokinetics of desmethyldiazepam and oxazepam (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 517-520 
    Details
    ISSN: 1432-1041
    Schlagwort(e): desmethyldiazepam ; oxazepam ; cimetidine ; hepatic elimination ; pharmacokinetics ; interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of single oral doses of desmethyldiazepam 20 mg or oxazepam 50 mg were studied in 5 healthy volunteers under controlled conditions, before and following a 24 h pretreatment with cimetidine 200 mg×5. Cimetidine significantly impaired (p=0.03) the elimination of desmethyldiazepam, as shown prolongation of its elimination half-life from 51.7±21.9 h to 72.6±39.4 h (mean ± SD), and a decrease in total plasma clearance from 12.0±2.7 ml/min to 8.6±3.3 ml/min. The disposition of oxazepam was not affected. From these results, and recently published data on diazepam and chlordiazepoxide, it is concluded that cimetidine impairs the hepatic elimination of those benzodiazepines which are metabolized by phase I reactions.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00874666
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  • 13
    Digitale Medien
    Digitale Medien
    An integrated study of pharmacokinetics and pharmacodynamics of chlormethiazole in healthy young volunteers (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 263-269 
    Details
    ISSN: 1432-1041
    Schlagwort(e): chlormethiazole ; pharmacokinetics ; pharmacodynamics ; sedatives ; blood concentrations ; amnesia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Chlormethiazole ethanedisulphonate (0.8%) (Hemineurin, Astra) was administered to 10 healthy unpremedicated volunteers at a constant-rate infusion of 2.5 ml/min for 60 min (Phase 1, n=5) and 113 min (Phase 2, n=5). With one exception, chlormethiazole blood concentration-time data were described by a two-compartment open model. Total body clearance was the same in both phases (1.15 l · min−1, SD 0.49; and 1.05 l · min−1, SD 0.36 respectively) and was similar to the clearance of indocyanine green. No correlation was found between clearance, initial dilution volume (137 l, SD 62; and 125 l, SD 33 in 1 and 2 phases respectively) or volume of distribution at steady-state equilibrium (308 l, SD 91; and 224 l, SD 59) with either body weight or estimated lean tissue mass. Slow half-life was 289 min (SD 169) in Phase 1 and 253 min (SD 172) in Phase 2. Moderately heavy sedation associated with amnesia while retaining the ability to readily obey verbal commands was achieved in one subject of Phase 1 and 4 subjects of Phase 2 and occurred at a mean chlormethiazole ethanedisulphonate blood concentration of 9.2 mg · l−1 (SD 2.9). Transient nasal irritation was experienced by all subjects during the initial stages of infusion. A rise in pulse rate (33%, SD 8) was a prominent feature but blood pressure and respiratory rates were very stable.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00562803
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  • 14
    Digitale Medien
    Digitale Medien
    The pharmacokinetics of intravenous and oral sulpiride in healthy human subjects (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 385-391 
    Details
    ISSN: 1432-1041
    Schlagwort(e): sulpiride ; pharmacokinetics ; serum clearance ; renal clearance ; bioavailability ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of sulpiride was studied in 6 healthy volunteers after intravenous and oral (tablets) administration of 100 mg. An open two- and in two subjects a three-compartment model was applied following intravenous administration. The average total distribution volume during the terminal slope was 2.72±0.66 l/kg and total systemic clearance was 415±84 ml/min. The serum half-life of the terminal slope following intravenous administration averaged 5.3 h (range 3.7–7.1 h) according to the two-compartment model. In two subjects the half-lives were 11.0 and 13.9 h when the three-compartment model was applied. Determination of urinary excretion rates of unchanged sulpiride indicated a half-life of 7.15 h. Following intravenous administration, 70±9% of the dose was recovered unchanged in urine within 36 h; the mean renal clearance was 310±91 ml/min. Sulpiride was absorbed slowly, with peak concentrations appearing between 3 and 6 h after oral administration. The recovery of unchanged drug in urine following oral administration was 15±5% of the dose, with a mean renal clearance of 223±47 ml/min. The bioavailability determined from combined plasma and urine data was only 27±9%. The low bioavailability was probably due to incomplete absorption.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00558453
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  • 15
    Digitale Medien
    Digitale Medien
    Clinical pharmacokinetics of alcuronium chloride in man (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 449-457 
    Details
    ISSN: 1432-1041
    Schlagwort(e): alcuronium ; single dose ; multiple dose ; plasma levels ; neuromuscular response ; pharmacokinetics ; anaesthesia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic behaviour of alcuronium is described for nineteen patients undergoing anaesthesia for elective surgery. Eleven patients received a single bolus intravenous dose of 0.25 mg/kg, while 8 patients required additional doses of 0.125 mg/kg. A two-compartment open model was found to describe adequately both the single dose and multiple dose data for the majority of patients. No significant differences were found in the model-independent pharmacokinetic parameters between the single and multiple dose studies. Mean values for the pooled data for the half-life (t1/2β), apparent volume of distribution (Vdβ), volume of distribution at steady-state (Vdss), volume of the central compartment (Vc) and plasma clearance (Clp) were 198.75 min, 24.261, 20.891, 8.181 and 90.22 ml/min respectively. Evoked muscle twitch response was monitored in 17 of the patients to assess the degree of relaxant blockade. The bolus dose of alcuronium produced complete block in 9 patients and between 95 and 99% block in the remainder. The time of onset to maximum block ranged from 3 to 30 min with the concurrently measured plasma levels of alcuronium being 0.79 to 2.25 µg/ml. The time taken following bolus administration to 5% recovery (95% paralysis) was a mean of 42 min and the corresponding mean alcuronium plasma concentration was 0.78 µg/ml.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00570163
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  • 16
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and dosage of digoxin in neonates and infants (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 69-74 
    Details
    ISSN: 1432-1041
    Schlagwort(e): digoxin ; neonates ; infants ; pharmacokinetics ; dosage schedules
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary As a therapeutic principle, a disease should be treated with the lowest effective dose of a drug. Accumulating information indicates that satisfactory contractile response of the myocardium is produced in young paediatric patients by doses of digoxin below existing recommendations. In addition, toxicity appears to be more frequent in neonates and infants treated with digoxin than previously thought. Therefore, dose calculations have been performed, based on pharmacokinetic parameters, with the aim of reaching and maintaining an average serum concentration of the glycoside of 2 nmol/l. This level is common in infants (〉1 month of age) during digoxin maintenance therapy and its adequacy is well supported by experience from adult cardiac patients. The calculations show that although current dosage schedules maintain the desired digoxin serum level in infants, they are often excessive for digitalization purposes. In neonates, the prevailing schemes do not sufficiently consider the immature state of the eliminating organs. Overdigitalization could therefore easily occur and continue in these patients, particularly in the premature newborns. This is in agreement with toxicity reports in the literature. The calculated doses should be less hazardous by being better adapted to the eliminating capacity of the various paediatric age-groups.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00561481
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  • 17
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of propranolol and sotalol in hyperthyroidism (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 373-377 
    Details
    ISSN: 1432-1041
    Schlagwort(e): propranolol ; sotalol ; thyrotoxicosis ; bioavailability ; serum tri-iodothyronine ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The elimination and bioavailability of two beta-blocking agents, propranolol and sotalol, were studied in 10 thyrotoxic patients, both before and after treatment with iodine-131. Each subject received in random order propranolol 160 mg and sotalol 160mg as single oral doses both while hyperthyroid and after euthyroidism had been achieved. The pharmacokinetics of sotalol was not affected by hyperthyroidism, whereas serum propranolol concentrations were significantly lower during hyperthyroidism than in the euthyroid state. During hyperthyroidism, the bioavailability of propranolol was significantly reduced (p〈0.05) and its clearance was increased (p〈0.005), whereas there was no difference in its serum t1/2. This indicates that the bioavailability of propranolol in hyperthyroidism is reduced by a mechanism which may depend on increased first-pass metabolism in the liver, or on an increased distribution volume of the drug. Both propranolol and sotalol caused a slight decrease in serum tri-iodothyronine concentration. As the effects of beta-blocking agents on the symptoms of hyperthyroidism are correlated with the serum concentration of the drugs, sotalol, with its long half-life and unaltered elimination in hyperthyroidism, has certain advantages over propranolol in the treatment of thyrotoxicosis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542321
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  • 18
    Digitale Medien
    Digitale Medien
    Studies of the different metabolic pathways of antipyrine in man (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 433-441 
    Details
    ISSN: 1432-1041
    Schlagwort(e): antipyrine ; antipyrine metabolites ; drug metabolism ; route of administration ; healthy volunteers ; urinary excretion ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of antipyrine in plasma and saliva, and urinary excretion of its major metabolites, were studied following i.v. and oral administration of antipyrine 500 mg to 6 healthy volunteers. Data from both plasma and saliva showed that the oral bioavailability of antipyrine given as an aqueous solution was complete. The saliva/plasma concentration ratio was constant with time from about 3 h onwards, with a mean value of 0.87 after oral and 0.91 after i.v. administration. It is concluded that the pharmacokinetic parameters of antipyrine can be satisfactorily established on the basis of salivary data, although the volume of distribution and clearance values are then slightly too high. After i.v. administration, 3.8±1.9% of the dose was excreted in urine as unchanged antipyrine in 48h, 24.9±6.3% as 4-hydroxyantipyrine, 16.5±3.2% as norantipyrine, 13.0±2.2% as 3-hydroxymethyl-antipyrine and 5.8±1.0% as 3-carboxy-antipyrine. No significant differences were observed following oral administration. The half-lives calculated from the linear part of the urinary excretion rate curves of the metabolites were about the same for oral and i.v. administration, and were of the same order of magnitude as the elimination half-life of parent drug in plasma and saliva. It is important for determination of the ultimate metabolite ratio that urine is collected for at least 36h, because there is a delay in the excretion of 3-hydroxymethyl-antipyrine in urine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542332
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  • 19
    Digitale Medien
    Digitale Medien
    Pharmacokinetic aspects of caffeine in premature infants with apnoea (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 47-52 
    Details
    ISSN: 1432-1041
    Schlagwort(e): apnoea ; caffeine ; premature infants ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of caffeine was examined in 13 premature infants (gestational age 25–34 weeks, birth weight 920–2060 g, postnatal age 1–42 days) who received the drug for treatment of opnoea. Caffeine (1% aqueous solution) was given i.v. in single doses; guided by the clinical response infants received between one and seven (mean 2.6) doses of 15 mg/kg. Mean (± SE; range) Clb was extremely slow − 8.5 ml/kg/h (±0.4; 5.8–12.2), t1/2 was prolonged − 65.0 h (±3.7; 48.2–87.5 h) and Vd was 0.781/kg (±0.04; 0.47–1.01). No significant correlation was found between Clb, t1/2 and postnatal age in the whole group or in individual infants. Effective plasma concentrations varied over a wide range (12–36 µg/ml) and overlapped with subtherapeutic concentrations (⩽24 µg/ml). Single doses of 15 mg/kg i.v. or p.o. prevented apnoea in most cases, if necessary followed by additional doses. Monitoring the blood level of caffeine in infants receiving frequent repeated doses is necessary to prevent toxicity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00606424
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  • 20
    Digitale Medien
    Digitale Medien
    Drug-related problems causing admission to a medical clinic (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 193-200 
    Details
    ISSN: 1432-1041
    Schlagwort(e): drug problems ; patient compliance ; adverse drug reactions ; interview ; pharmacokinetics ; inadequate therapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The association between hospital admission and drug-related problems was evaluated in 285 consecutive admissions to two medical wards in a Swedish university hospital. Standardised definitions and criteria for causality were used. A drug-related problem was judged to have been the main reason for admission of 36 patients, and a strongly contributory reason for 9. These 45 patients comprised 16% of all patients, and 19% of those receiving medication prior to admission. For 19 patients the problem was considered to be failure to achieve the desired therapeutic effect. 11 of these 19 took less medication than prescribed, and an inadequate dose had been presented for the other 8 patients. In 26 patients there was an excessive or otherwise adverse effect. In 10 it was an intentional or accidental poisoning, and 16 had an adverse drug reaction. Non-compliance with the prescribed regimen caused almost half of the drug-related admissions: 11 took too little and 10 took too much of the prescribed drugs. The majority of the other problems could probably have been prevented by better application of pharmacokinetic principles to the prescribing.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00544597
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  • 21
    Digitale Medien
    Digitale Medien
    Disposition of intravenous diazepam in young men and women (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 207-213 
    Details
    ISSN: 1432-1041
    Schlagwort(e): diazepam ; benzodiazepines ; N-desmethyldiazepam ; plasma ; saliva ; pharmacokinetics ; pharmacodynamics ; psychomotor ; impairment ; oral contraceptives
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The disposition of a single intravenous dose of diazepam (10 mg) was studied in 11 young, healthy subjects (6 males and 5 females on oral contraceptives). Plasma samples were obtained over 28 days and diazepam and N-desmethyldiazepam plasma concentrations and diazepam free fractions were determined. The salivary excretion of diazepam and N-desmethyldiazepam was studied over 72 h. A series of psychomotor performance tests were administered over the first 8 h. Interindividual variation in mean diazepam disposition over time is not principally related to variation in plasma protein binding; 93% of the variation in clearance is accounted for by variation in intrinsic clearance. Interindividual variation in diazepam disposition is modest but the plasma clearance of diazepam in women on oral contraceptives (median 14.0 ml/min) is significantly (p=0.004) less than in men (median 23.4 ml/min) and the area under the curve (AUC) of diazepam is highly correlated with the AUC of the principal active metabolite (r=0.90, p〈0.001). The AUC of N-desmethyldiazepam (median 9.2 µg·h/ml) in women is greater (p=0.06) than in men (median 7.5 µg·h/ml). On chronic administration of diazepam, therefore, women taking oral contraceptives will have greater plasma concentrations per unit dose of both diazepam and N-desmethyldiazepam than men. The clearance of diazepam in control groups of 11 young men (median 23.8 ml/min) and 10 young women not taking oral contraceptives (median 26.8 ml/min) is not significantly different. Plasma and salivary concentratrions of diazepam are correlated (p〈0.001) but the predictive value of this correlation is limited (r=0.70) since the ratio of salivary to plasma concentrations varies significantly over the day. The use of calculated free diazepam plasma concentrations does not improve the correlation (r=0.68) but the slope of this regression (1.00) is that predicted by theory.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00544599
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  • 22
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of parenteral paracetamol and its analgesic effects in post-operative dental pain (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 215-218 
    Details
    ISSN: 1432-1041
    Schlagwort(e): paracetamol ; acetaminophen ; dental pain ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A double-blind, randomised, crossover trial was undertaken to compare the analgesic effects of a single dose of paracetamol (1000 mg i. v.) with placebo in the immediate post-operative period following removal of impacted lower third molars. There was no significant difference in the pain relief between paracetamol and placebo in the first hour following injection. Thereafter, there was significantly less pain (P〈0.05) after treatment with paracetamol than after placebo. Plasma concentrations of paracetamol were measured and pharmacokinetic variables were determined. Over the four hour period of investigation there was no clear relationship between analgesia and paracetamol concentration in either central or peripheral compartments.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00544600
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  • 23
    Digitale Medien
    Digitale Medien
    Does cantharides blister fluid provide access to the peripheral compartment? (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 327-330 
    Details
    ISSN: 1432-1041
    Schlagwort(e): bendroflumethiazide ; cantharides plasters ; blister fluid ; plasma levels ; pharmacokinetics ; compartmental analysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of bendroflumethiazide (BFT) was investigated following the oral administration of 10 mg to 3 healthy volunteers. Each subject participated twice in the study. BFT was determined in plasma and cantharides blister fluid from 1/2 to 30 h post administration. Blister fluid was obtained from blisters 10–22 h old. Plasma levels were fitted to a tri-exponential equation and the concentration of the drug in the peripheral compartment was calculated from the microscopic rate constants. In 5 of 6 cases investigated, cantharides blister fluid levels paralleled the concentration of the drug in the peripheral compartment. The mean blister fluid levels exceeded the calculated concentration in Compartment 2 1.46 fold. In one case, the blister fluid level paralleled the plasma level. This subject clearly differed from the others as more than 10 h were required for blister formation in her. The results suggest that following the administration of BFT, cantharides blister fluid behaves as part of the peripheral compartment. The possible value of studying blister fluid levels in pharmacokinetic investigations is discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613614
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  • 24
    Digitale Medien
    Digitale Medien
    The influence of free fatty acids on valproic acid plasma protein binding during fasting in normal humans (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 343-347 
    Details
    ISSN: 1432-1041
    Schlagwort(e): valproic acid ; fatty acids ; plasma protein binding ; pharmacokinetics ; drug metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of physiologic variations of free fatty acid levels on in vivo valproic acid plasma protein binding was studied in 6 healthy adult subjects. 14 blood samples were taken during a 12-h dosing interval at steady state while in a fed condition and also during a 27 h fast. Free fraction and total valproate concentration were determined by equilibrium dialysis and GLC, respectively. Free fatty acid levels were determined from both fresh samples and samples incubated at 37°C for 12 h, the latter in order to simulate equilibrium dialysis conditions. Fasting resulted in increased serum free fatty acid levels in all subjects, ranging from 34–182% (p〈0.01). Incubation also caused free fatty acid levels to rise, more so in fed samples (50–87%,p〈0.01) than in fasting samples (10–50%,p〈0.01). Fasting resulted in a 9% increase in the mean free fraction for all subjects combined (p〈0.01). Regression analysis of 180 sets of values for free fraction, total valproate concentration and free fatty acid level suggested that valproate concentration accounts for 17% and free fatty acid level for 37% of the variation in free fraction. Mean clearance was unchanged by fasting despite an increased free fraction suggesting decreased intrinsic clearance (i.e. decreased metabolism) of valproate under these conditions.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613618
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  • 25
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of pancuronium in man: A linear system (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 369-372 
    Details
    ISSN: 1432-1041
    Schlagwort(e): neuromuscular blockade ; pancuronium ; non-depolarizing neuromuscular blocking agent ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Pancuronium in bolus doses of 40 to 350 µg/kg was administered to surgical patients in order to evaluate the linearity of its pharmacokinetics. The profile of the plasma decay curve and of its urinary elimination were compared with reference to the administered dose. It was possible to superimpose the dose-normalized plasma decay-curves. The parameters of the two compartment-open model used to describe the pharmacokinetics of pancuronium were not influenced by the dose. The elimination half-life was 89±20 min and the plasma clearance was 1.84±0.38 ml/min/kg. The profiles of cumulative urinary excretion were also dose-independent. After 6 and 24 h, 57% and 69% of the administered dose, respectively, had been excreted in the urine. The results indicate that the pharmacokinetics of pancuronium is linear.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613623
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  • 26
    Digitale Medien
    Digitale Medien
    Overdosage of antidepressants: Clinical and pharmacokinetic aspects (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 513-521 
    Details
    ISSN: 1432-1041
    Schlagwort(e): amitriptyline ; imipramine ; clomipramine ; antidepressant overdose ; clinical effects ; pharmacokinetics ; cardiotoxicity ; maprotiline ; doxepine ; nortriptyline ; opipramol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Twenty-nine cases of self-poisoning with antidepressants (amitriptyline, imipramine, clomipramine, maprotiline, doxepine, nortriptyline, opipramol) were examined by frequent observation of CNS effects, heart rate, blood pressure and standard ECG, 24 h-ECG-monitoring, measurement of systolic time intervals, EEG recordings and frequent measurement of serum levels of antidepressants and primary metabolites. None of the patients died. Maximum total serum antidepressant level (parent compound + desmethyl metabolite) ranged from 20 to 2200 µg/l, with concentrations above 500 µg/l in 11 cases. The serum amitriptyline concentration remained high for 3–4 days in some of the severely intoxicated patients and the decay curves were compatible with partly saturated elimination. A degree of unconsciousness and the occurrence of excitation and hallucinations were generally seen in cases with total serum antidepressant levels above 500 µg/l. Grand mal seizures occurred more frequently at high antidepressant levels, but could not be predicted from the EEG recordings. Increased heart rate and prolonged QRS- and QTc-intervals were significantly correlated with the total serum antidpressant level. 24 h-ECG-monitoring revealed no serious arrhythmias or instances of heart block. Hypotension was only seen initially in few patients. Systolic time interval measurements showed changes suggesting impaired myocardial performance (elevated PEP/LVET ratio) at intermediate (60–500 µg/l) but not high (〉500 µg/l) total serum antidepressant levels. Measurement of serum concentration in antidepressant intoxication is important for identification of patients with high serum levels and the corresponding risk of developing toxic reactions, and to exclude patients with a low concentration who do not require intensive observation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00637499
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  • 27
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and tolerance of slow-release indomethacin tablets in rheumatoid arthritis (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 349-351 
    Details
    ISSN: 1432-1041
    Schlagwort(e): indomethazine ; rheumatoid arthritis ; pharmacokinetics ; tolerance ; side effects ; slow-release tablets
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics, efficacy and tolerance of a new formulation of slow-release indomethacin tablet were compared with those of a conventional indomethacin capsule in 30 patients with rheumatoid arthritis. The slow-release tablet was absorbed more slowly than the capsule (tmax 3.7 h and 〈 2 h, respectively) and produced more even serum drug levels in 10 subjects. Side-effects, especially dizziness and diarrhoea, were less frequent after the slow-release tablet than during the capsule period.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613619
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  • 28
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of theophylline in Ethiopian children of differing nutritional status (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 89-92 
    Details
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; kwashiorkor ; marasmus ; children ; nutritional status ; pharmacokinetics ; dosage recommendation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of theophylline in Ethiopian children of differing nutritional status was studied. In 8 children of normal weight, the t1/2β (4.93 h) plasma clearance (1.22 ml/min/kg and Vd area (504 ml/kg) were similar to those of Swedish children of normal weight. In children with marasmus or kwashiorkor there was an increased volume of distribution. The increase in Vd was reflected in an increased biological half-life, in spite of a slight but not significant increase in clearance in both of these groups of children. The pharmacokinetic changes in clearance and volume of distribution found in malnutrition should counteract each other, so from a clinical point of view theophylline can be given to Ethiopian children according to the standard dosage recommendation, regardless of nutritional status.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613932
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  • 29
    Digitale Medien
    Digitale Medien
    Bioavailability and pharmacokinetics of theophylline in plain uncoated and sustained-release dosage forms in relation to smoking habit I. Single dose study (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 79-87 
    Details
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; smoking habit ; absolute bioavailability ; pharmacokinetics ; sustained release preparation ; plain tablet preparation ; antipyrine pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The bioavailability and pharmacokinetics of theophylline from a plain uncoated and 2 newly designed, sustained-release tablet formulations, as compared to intravenous aminophylline, were studied in 12 healthy adult male volunteers. The subjects were divided into two groups (n=6) with respect to smoking habit and on 4 separate occasions each received, on a randomized cross-over basis, a single dose of 400 mg equivalent of theophylline from every dosage form. The intravenous aminophylline study showed that habitual smoking had a significant (p〈0.05) effect on plasma theophylline clearance (0.051±0.006 vs 0.035±0.004 l/kg/h). Smoking significantly reduced the raw AUC from the 4 dosage forms (p〈0.05), but did not change the characteristics of absorption of each formulation. There was a non-significant trend towards reduced absolute bioavailability of theophylline from sustained-release formulations in smokers (percentage mean difference — 16% for one formulation and 13% for another). The trend was not observed for the plain uncoated tablet, which was rapidly absorbed (p〈0.01 to 0.05 in Ka, tmax and Cmax compared to sustained-release tablets). Similarity of the in vitro dissolution profiles of the two sustained-release formulations did not imply similarity of the in vivo absorption characteristics. Plasma clearances of theophylline and antipyrine were significantly correlated (p〈0.05,r=0.693,n=10). Thus, smoking enhanced the elimination of theophylline regardless of the dosage form administered. However, the extent to which habitual smoking may affect the hepatic first-pass effect on theophylline from sustained-release formulations requires further study. The results also suggest that theophylline and antipyrine may share a similar or common and presumably polycyclic hydrocarbon-inducible form(s) of microsomal drugmetabolizing enzyme.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613931
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  • 30
    Digitale Medien
    Digitale Medien
    Bioavailability of oral dexamethasone during high dose steroid therapy in neurological patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 103-108 
    Details
    ISSN: 1432-1041
    Schlagwort(e): dexamethasone ; bioavailability ; pharmacokinetics ; ‘first-pass’ effect ; pre-systemic elimination
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and oral biovailability of dexamethasone were studied in 6 patients with neurological disease being treated with high dosages of the drug. A specific high performance liquid chromatographic assay was used to measure dexamethasone concentrations. Unlike the previously published mean figure of 0.78 for the oral bioavailability of the drug given in single doses to healthy volunteers, the mean bioavailability of dexamethasone in the patients studied was 0.53±SD 0.40. It appeared more likely that this incomplete bioavailability was due to presystemic elimination than to poor absorption. The intravenous clearance of the drug was relatively high (0.4902±SD 2291 l kg−1, approximately 65% of expected hepatic plasma flow), the oral clearance higher (2.5804±SD 3.2181 l kg−1 h−1) while the absorption rate constant (4.8729±8.4998 h−1), suggested rapid absorption after oral administration. Prior phenytoin and possibly prior dexamethasone therapy is likely to have contributed to the higher clearance values of the drug in these patients than the values reported in healthy volunteers after single dose studies.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613935
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  • 31
    Digitale Medien
    Digitale Medien
    Pharmacodynamic and pharmacokinetic evaluation in man of the new sympathomimetic amezinium (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 185-190 
    Details
    ISSN: 1432-1041
    Schlagwort(e): amezinium ; hypotension ; antihypotensive drug ; ECG ; concentration-effect relationship ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Blood pressure, ECG and plasma concentration were determined for up to 12h following single i.v. (10 mg) and oral (20 mg) doses of amezinium (Regulton®) in 8 healthy, male volunteers. The i.v. and oral doses were almost equi-active in significantly increasing systolic blood pressure (SBP) by 14.5 and 15.6 mmHg, respectively. The maximum SBP after the i.v. dose was reached after 45 min, and 105 min after oral administration. The heart rate fell reflexly. The increases in mean and diastolic blood pressures were not significant. Pulse pressure was enhanced after both i.v. and oral administration. The effect on systolic blood pressure lasted for about 4 h. There was a slight shortening of the QTc duration, which could not be explained as a drug effect. Other ECG time intervals were not altered. Multiple regression analysis showed a significant positive correlation between the log plasma concentration and the increase in SBP between 0.5 and 5 h after oral administration (r=0.78,p〈0.001) and between 0.75 and 5 h after i.v. administration (r=0.83,p〈0.001). 30 min after amezinium p.o. the mean SBP began to rise, when a plasma level of about 30 ng/ml was reached.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613815
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  • 32
    Digitale Medien
    Digitale Medien
    Plasma levels of sulfinpyrazone and of two of its metabolites after a single dose and during the steady state (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 231-235 
    Details
    ISSN: 1432-1041
    Schlagwort(e): sulfinpyrazone ; pharmacokinetics ; metabolites ; inhibition of platelet aggregation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of sulfinpyrazone, and the plasma levels of its sulfide and sulfone metabolites, have been determined after a single oral dose (400 mg) and during steady-state conditions (4×200 mg daily for 6 days) in healthy female volunteers. The plasma half-lives of sulfinpyrazone, the sulfone and the sulfide were 3.7, 3.2 and 14.7 h, respectively, during steady-state. After a single dose and during steady state conditions the half-lives of sulfinpyrazone and the sulfone did not differ significantly. The trough plasma levels of the sulfide metabolite exceeded those of the parent compound in four of the six volunteers on the last day of the study. The data suggest that in man the most likely candidate for the prolonged inhibition of platelet aggregation observed after treatment with sulfinpyrazone is its sulfide metabolite, because of its prolonged elimination.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613823
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  • 33
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of chlorambucil in man after administration of the free drug and its prednisolone ester (prednimustine, Leo 1031) (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 251-253 
    Details
    ISSN: 1432-1041
    Schlagwort(e): chlorambucil ; prednimustine ; plasma concentrations ; bioavailability ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of chlorambucil has been investigated in a cross over study after oral administration of the free drug (10 mg) and its prednisolone ester (prednimustine, 100 mg). The bioavailability of chlorambucil was about five times lower when given as prednimustine as compared to administration of the free drug. The peak plasma concentration was about twice as high and it was obtained more rapidly when the free drug was given. No intact prednimustine could be detected in plasma.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613827
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  • 34
    Digitale Medien
    Digitale Medien
    Clinical effect and pharmacokinetics of trimethoprim-sulphadiazine in children with urinary tract infections (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 267-271 
    Details
    ISSN: 1432-1041
    Schlagwort(e): trimethoprim ; sulphadiazine ; urinary tract infection ; children ; pharmacokinetics ; urinary concentrations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The clinical effect and pharmacokinetics of the combination trimethoprim (TMP)-sulphadiazine (SD) were studied in 18 children with acute urinary tract infections (UTI), aged 2–56 months. A suspension of TMP-SD (9+41 mg/ml) was taken orally twice daily for 10 days. Various doses of TMP (2.9–3.7 mg/kg/day) and SD (12.9–16.7 mg/kg/day) were also given to children of different ages. After 2–4 days of treatment, bacterial cultures of urine were negative and C-reactive protein in serum, WBC count and ESR in all patients had become normal. Steady state serum levels for both components were reached after 4 or more days of treatment. At steady state, mean peak serum concentrations of TMP and SD of 1.4 µg/ml and 27 µg/ml, respectively, were found within 2–4 h after a fasting morning dose. The biological half-lives of TMP and SD were of the same order of magnitude, but the total clearance of TMP was 5 times greater than that of SD. The concentrations of TMP-SD in urine were invariably more than 10 times the minimum inhibitory concentrations (MIC) for the causative organisms (tested at the ratios 1:20 and 1:4 of TMP and SD). Non-metabolized SD constituted 77% of total SD in urine of infants, and 55% of total SD in children of 1 year or more. The TMP-SD combination showed a satisfactory clinical effect and favourable pharmacokinetic properties in children with UTI.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613830
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  • 35
    Digitale Medien
    Digitale Medien
    Disposition and clinical pharmacokinetics of theophylline after administration of a new sustained release tablet (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 39-44 
    Details
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; sustained release tablet ; absolute bioavailability ; pharmacokinetics ; individual dosage regimen
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The systemic disposition of theophylline after taking a new, sustained release tablet (Theolair Retard® 250 mg, Theolair S. R.®, Riker Laboratories) has been studied in 8 hospitalized patients. Absolute bioavailability was determined from the ratios of the areas under the serum concentration-time curves after intake of the tablet and after intravenous infusion of aminophylline in the same patient. The absolute bioavailability of Theolair Retard® 250 mg was 110.9±20.8% (mean ± SD). Maximal serum concentrations were reached after 7.3±3.5 h, the large intersubject variation being due to differences in gastric emptying time. The tablets appear to release theophylline slowly in acid conditions, but more rapidly in an alkaline medium. Invasion was found to be either monophasic with a rate constant of about 0.8 h−1 (intestine), or biphasic with rate constants of 0.2 h−1 (stomach) and 0.8 h−1 (intestine). The peak levels accounted for 7.9±2.2 mg · 1−1. The profiles of the serum concentration-time curves were such that the concentrations remained above 80% of cmax for 6.5±3.3 h. The relevant pharmacokinetic parameters (half-life of elimination, total body clearance and volume of distribution) were determined and were used to calculate the individual dosage regimens required to obtain therapeutic serum concentrations. The optimal dosing interval to obtain an average steady state serum concentration of 12.5 mg · l−1 was 9.8±3.1 h.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609586
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  • 36
    Digitale Medien
    Digitale Medien
    May mothers taking acenocoumarol breast feed their infants? (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 61-64 
    Details
    ISSN: 1432-1041
    Schlagwort(e): acenocoumarol ; anticoagulant therapy ; breast feeding ; breast milk ; neonatal thrombotest ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 20 women receiving Sintrom® post partum, the acenocoumarol concentration in serum and breast milk at different times was measured. Even at the time of maximal serum concentration, or for the following 6 h, no acenocoumarol could be detected in the breast milk. In accordance with this finding, no effect of breast feeding on Thrombotest values of the infants could be demonstrated. These data suggest that mothers taking acenocoumarol for a short period may safely breast feed their infants.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609589
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  • 37
    Digitale Medien
    Digitale Medien
    Plasma and salivary pharmacokinetics of caffeine in man (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 45-52 
    Details
    ISSN: 1432-1041
    Schlagwort(e): caffeine ; pharmacokinetics ; plasma ; saliva ; urinary elimination
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma and salivary caffeine concentrations were measured by gas-liquid chromatography in 6 healthy caffeine-free volunteers following oral administration of 50, 300, 500 and 750 mg caffeine. Caffeine was also given to a single subject intravenously in doses of 300, 500 and 750 mg. Caffeine was rapidly absorbed and was completely available at all doses. The apparent first-order elimination rate constant decreased linearly with dose and was 0.163±0.081 h−1 for 50 mg and 0.098±0.027 h−1 for 750 mg. The total body clearance was unaffected by dose and was 0.98±0.38 ml/min/kg. There was a trend towards increasing apparent volume of distribution with increasing dose. A linear relationship existed between the area under the plasma concentration, time curve and dose and dose-normalised plasma concentration, time plots were superimposable. These findings suggest that caffeine obeys linear pharmacokinetics over the dose range investigated. Despite significant inter-individual differences in pharmacokinetic parameters there was good reproducibility within 5 subjects given 300 mg caffeine orally on 3 occasions. Salivary caffeine levels probably reflect the unbound plasma caffeine concentration and can be used to estimate the pharmacokinetic parameters of the drug. Overall the saliva/plasma concentration ratio was 0.74±0.08 but within subjects some time-dependence of the ratio was found with higher ratios initially (even after intravenous administration) and lower ratios at longer time intervals after the dose. Urinary elimination of caffeine was low and independent of dose: 1.83% of the dose was eliminated unchanged.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609587
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  • 38
    Digitale Medien
    Digitale Medien
    The effects of peritoneal dialysis on the single dose and steady state pharmacokinetics of valproic acid in a uremic epileptic child (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 387-390 
    Details
    ISSN: 1432-1041
    Schlagwort(e): valproic acid ; epilepsy ; uremia ; pharmacokinetics ; peritoneal dialysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of valproic acid (VPA) have been studied during peritoneal dialysis in a uremic male epileptic child following a single 500 mg dose and after multiple doses over 5 months (700 mg daily) of valproic acid as the syrup. Serum level decline was biphasic in both instances with a terminal half-life of 27.2 h after the single dose and 10.2 h at steady-state. Total serum clearance was 0.0236 l/h/kg after the single dose and increased to 0.0408 l/h/kg after 5 months. Free (intrinsic) serum clearances were 0.1489 and 0.1518 l/h/kg and serum free fractions were 0.224 and 0.272 respectively for the single dose and steady-state studies. Peritoneal dialysis for periods of 12 or 24 h removed an average of 4.5% of the VPA dose.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00610060
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  • 39
    Digitale Medien
    Digitale Medien
    The pharmacokinetics of ranitidine in patients with chronic duodenal ulceration: A comparison of responders and non-responders (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 441-447 
    Details
    ISSN: 1432-1041
    Schlagwort(e): ranitidine ; duodenal ulceration ; pharmacokinetics ; non-responders ; therapeutic response ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of orally administered ranitidine were studied in 17 male patients with chronic duodenal ulceration. The patients were divided into 2 groups, 10 responders and 7 nonresponders, on the basis of their endoscopic response to ranitidine treatment. The 10 responders were studied both after a single 150 mg dose (SD) and after multiple dosing (MD) with ranitidine 150 mg twice daily for 4 weeks. The area under the curve (AUC) and maximum concentration (Cmax) were significantly higher (p〈0.01 andp〈0.05, respectively) after MD than after SD, but the half-life (t1/2) and minimum concentration (Cmin) 12 h postdosing did not differ. The non-responders were studied after MD only and their pharmacokinetic characteristics were compared with those of responders. No differences between the 2 groups were found. However, 2 non-responders had particularly low plasma ranitidine levels and high acid output. Such patients may need larger doses of ranitidine for adequate suppression of gastric acid. Five patients (4 responders and 1 non-responder) received ranitidine 20 mg i.v. The drug followed a two-compartment model, with mean values for t1/2β, volume of distribution steady-state and total plasma clearance of 80 min, 701 and 680 ml/min, respectively. The oral bioavailability of ranitidine in these 5 patients showed wide variation (27–76%; mean 51%).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609883
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  • 40
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of tocainide in patients with renal dysfunction and during haemodialysis (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 503-507 
    Details
    ISSN: 1432-1041
    Schlagwort(e): tocainide ; pharmacokinetics ; renal failure ; antiarrhythmic drug ; haemodialysis ; cirrhosis ; acetyldigoxin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The disposition of tocainide was studied in 15 patients with renal dysfunction. In 9 with total renal failure, the plasma half-life ranged from 16.6 to 42.7 h and total plasma clearance from 35 to 94 ml/min. The longest half-lives were found in 1 patient with cirrhosis, 3 taking the enzyme inhibitor allopurinol, and 1 on cimetidine. The mean half-life in the remaining patients was 22.3±4.8 h (±SD). During a 4 h haemodialysis, the half-life in the 9 patients decreased to 8.5±4.6 h, which was calculated to correspond to removal of 25±14% of the drug from the body. In 6 patients with impaired renal function (creatinine clearance 10–55 ml/min) the tocainide half-life ranged from 13.2 to 22.0 h and total plasma clearance from 72 to 122 ml/min. One patient was taking allopurinol and 1 dihydralazine, and the mean half-life in the others was 19.2±4.0 h. The apparent volume of distribution was similar to that found previously in healthy subjects. The results suggest that tocainide elimination is predictably reduced in patients with renal disease.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609893
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  • 41
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of sotalol during pregnancy (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 521-524 
    Details
    ISSN: 1432-1041
    Schlagwort(e): sotalol ; beta-adrenoceptor antagonist ; pregnancy ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Sotalol, a beta-adrenoceptor blocking drug, was administered to 6 healthy pregnant volunteers between 32–36 weeks gestation and when at least 6 weeks post-partum. On both occasions, each volunteer was given sotalol 100 mg intravenously and 400 mg orally in randomised order with at least a 1 week washout period between. Plasma samples were analysed for sotalol using a fluorometric method and the pharmacokinetic profiles investigated. The systemic clearance of sotalol was significantly greater in the antenatal period (2.4±0.3 ml/min/kg) than in the post-natal phase (1.5±0.1 ml/min/kg). The apparent volume of distribution was similar in the two periods: the elimination half-life was 6.6±0.6h ante-natally and 9.3±0.7h post-natally after intravenous drug but the trend for faster elimination was not significant. The elimination half-life after oral administration (about 10h) and bioavailability (about 90%) were not altered significantly by pregnancy. It is suggested that the more rapid clearance of sotalol in pregnancy may be due to increases in renal plasma flow and glomerular filtration rate.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609896
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  • 42
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of tryptophan, renal handling of kynurenine and the effect of nicotinamide on its appearance in plasma and urine following L-tryptophan loading of healthy subjects (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 137-142 
    Details
    ISSN: 1432-1041
    Schlagwort(e): tryptophan ; pharmacokinetics ; kynurenine ; 3-hydroxykynurenine ; renal clearance ; nicotinamide ; tryptophan pyrrolase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of tryptophan, the temporal occurence of kynurenine (KYN) and 3-hydroxykynurenine (3-HK) in plasma and urine, and the effect of nicotinamide on tryptophan metabolism were studied in 6 healthy subjects after oral administration of L-tryptophan 100 mg per kg body weight. The peak concentration of tryptophan in plasma occurred after 1 to 2 h, tryptophan disappeared linearly from 2 to 5 h and exponentially from 5 to 8 h. Urinary tryptophan excretion was negligible. The peak concentration of KYN in plasma occurred after 4 h and it was correlated significantly with the area under the plasma curve (AUC) of KYN of the subjects investigated. The AUC in plasma of KYN was significantly correlated with urinary KYN excretion within individuals, but not in the group as a whole. The data suggest that KYN was reabsorbed by renal tubules and that the degree of reabsorption was subject to large interindividual variation. The peak concentration in plasma of 3-HK occurred 11 min later than that of KYN. The results suggest that the net tubular effect on 3-HK was secretion. Pre-treatment with nicotinamide (0.5 g three times daily) resulted in considerable decreases in AUC in plasma, and in urinary excretion of KYN and 3-HK, indicating inhibition of liver tryptophan pyrrolase. The concomitant increase in AUC in plasma of free and total tryptophan was insignificant. As only a relatively small amount of tryptophan is catabolized by tryptophan pyrrolase following an L-tryptophan load, cautious interpretation is recommended of urinary KYN excretion as an indicator of tryptophan break down in investigation of different subjects.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00637514
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  • 43
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of bupropion, a novel antidepressant agent, following oral administration to healthy subjects (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 127-135 
    Details
    ISSN: 1432-1041
    Schlagwort(e): antidepressant ; bupropion ; pharmacokinetics ; oral administration ; radioimmunoassay ; urinary excretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of bupropion hydrochloride, a structurally novel antidepressant agent, have been studied in healthy male and female subjects following administration of single oral doses of 50, 100 and 200 mg. Plasma drug concentrations were determined directly by a specific radioimmunoassay (r. i. a.), while urinary measurements required a prior solvent extraction to remove substances interfering in the assay. Bupropion appeared rapidly in the plasma, suggesting good absorption. Drug plasma concentration-time data were fitted well to a two-compartment open model of drug disposition by use of the computer program NONLIN. By comparison of AUC, Cmax and tmax values, the pharmacokinetics of bupropion were found to be linear across the 50–200 mg dose range in both sexes. When the data were normalized for subjects' body weights, no differences between pharmacokinetic parameters for male and female subjects were found. Mean disposition half-lives across treatments were 1.2–1.4 h for t1 2α and 10.7–13.8 h for the t1 2β. Bupropion was extensively bound (85%) to human plasma proteins over a wide drug concentration range. Less than 1% of a 200 mg oral dose of bupropion hydrochloride appeared in the urine of 16 subjects as unchanged drug, indicating extensive metabolism of the parent compound.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00637513
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  • 44
    Digitale Medien
    Digitale Medien
    Chloramphenicol pharmacokinetics in Ethiopian children of differing nutritional status (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 819-823 
    Details
    ISSN: 1432-1041
    Schlagwort(e): chloramphenicol ; children ; pharmacokinetics ; oral dose ; absorption ; i.v. dose ; kwashiorkor ; marasmus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of i.v. chloramphenicol succinate and oral chloramphenicol palmitate were studied in Ethiopian children with different nutritional states. In children with kwashiorkor the plasma clearance of chloramphenicol was significantly lower than in children of normal weight (4.16 ml/min/kg versus 7.53 ml/min/kg). In consequence the mean half-life was prolonged (3.76 h versus 2.85 h) and this led to somewhat higher plasma levels in the kwashiorkor children. The influence of the pathophysiological changes offset one another so that plasma concentrations within the therapeutic range were obtained in children with kwashiorkor given recommended standard i.v. doses. The absorption of chloramphenicol after oral administration in severely malnourished children was erratic, which suggests that this route should be avoided in such patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00607094
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  • 45
    Digitale Medien
    Digitale Medien
    Proof of the linearity of the pharmacokinetics of alinidine in man (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 201-207 
    Details
    ISSN: 1432-1041
    Schlagwort(e): alinidine ; pharmacokinetics ; radioimmunoassay ; computer model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of alinidine was investigated in two groups of volunteers: Group I (N=5) received on two different occasions single doses of14C-labelled drug given orally (40 mg) or intravenously (10 mg); Group II (N=6) received single oral doses 10, 30 or 90 mg dissolved in 20 ml water. The samples from Group I were analysed by two different and independent methods (RIA and counting total radioactivity). The results obtained by the two methods were identical, since the compound was not metabolized. The plasma concentrations and renal excretion data obtained from both groups were individually fitted to an open three compartment model. Independent of the route of administration and of the doses given, similar pharmacokinetic parameters were calculated for each group and each trial. The half lives of the distribution and elimination phases were t1/2α: 36–41 s, t1/2β : 9.9–11.1 min and t1/2γ: 2.7–3.8 h. There was a linear relationship between the dose administered and the resulting areas under the plasma concentration curves (AUC). Following a lag period (τ=0.19–0.22 h), the peak plasma concentration was reached 0.6–1.2 h after oral administration. Oral alinidine was 100% bioavailable.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00627921
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  • 46
    Digitale Medien
    Digitale Medien
    Effect of ethanol intake on disopyramide elimination by healthy volunteers (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 103-105 
    Details
    ISSN: 1432-1041
    Schlagwort(e): disopyramide ; ethanol ; pharmacokinetics ; interaction ; metabolic clearance ; renal clearance ; diuresis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of ethanol intake on disopyramide elimination was examined in an open cross-over study in six healthy volunteers. No effect of ethanol on the elimination half-life or total body clearance of disopyramide was found, although it did decrease the percentage of mono-N-dealkylated disopyramide excreted in the urine (p〈0.05) as well as the relative metabolic clearance of disopyramide (p〈0.05). The renal clearance of disopyramide was increased by 19±16% (p〈0.05) in subjects in whom ethanol caused a diuresis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00544024
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  • 47
    Digitale Medien
    Digitale Medien
    Pharmacokinetic aspects of guanfacine withdrawal syndrome in a hypertensive patient with chronic renal failure (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 463-466 
    Details
    ISSN: 1432-1041
    Schlagwort(e): guanfacine ; hypertension ; phenobarbital ; withdrawal syndrome ; enzyme induction ; pharmacokinetics ; renal insufficiency
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The unusual observation of a withdrawal syndrome due to guanfacine in a hypertensive patient with chronic renal failure led to a study of the kinetics of the drug in this patient. The principal pharmacokinetic parameters of guanfacine were greatly altered, with extended biotransformation and a decrease in the half-life compared to the values observed in other cases of severe renal insufficiency. Associated treatment with phenobarbital had had a considerable effect, as shown by the results of a further kinetic study 2 months after withdrawal of the phenobarbital. The findings then were in good agreement with reference values which strongly suggests a consequence of the enzyme inducing effect of phenobarbital. Advice about the dosage regimen in such cases is given.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542112
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  • 48
    Digitale Medien
    Digitale Medien
    Disposition of 5-aminosalicylic acid, the active metabolite of sulphasalazine, in man (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 511-515 
    Details
    ISSN: 1432-1041
    Schlagwort(e): 5-aminosalicylic acid ; inflammatory bowel disease ; sulphasalazine disposition ; pharmacokinetics ; healthy volunteers ; urinary excretion ; biliary excretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The disposition of 5-aminosalicylic acid (5-AS), the therapeutically active metabolite of sulphasalazine (SZ), has been studied in patients with active inflammatory bowel disease, in patients with biliary tract disease and post-operative T-tube drainage, and in healthy volunteers. Subjects were treated 3 times a day either with 5-AS 0.5 g suppositories and a slow-release preparation or with SZ 1 g tid (equivalent to 5-AS 1.14 g/day). Plasma and urine concentrations of 5-AS and its acetylated major metabolite (AcAS) were monitored during one dosing interval. In a cross-over trial in 5 patients with ulcerative colitis no difference, was found in the dose-corrected mean (± SD) steady state plasma levels (Css) of 5-AS and AcAS between treatment with 5-AS suppositories (0.10±0.07 and 0.50±0.20 µg/ml, respectively) and SZ (0.12±0.14 and 0.67±0.14 µg/ml, respectively). Urinary excretion of total AS (5-AS+AcAS), too, was similar (192±70 and 179±79 mg/day) with both forms of treatment. The oral slow-release form of 5-AS produced slightly higher Css in 5 patients with Crohn's disease (5-AS 0.21±0.22 µg/ml; AcAS 0.83±0.40 µg/ml) and in 5 healthy volunteers (5-AS 0.28±0.14 µg/ml; AcAS 1.10±0.43 µg/ml). Urinary recovery of total AS averaged 20±6% (patients) and 27±10% (volunteers). The cross-over trial in 7 patients with a biliary T-tube revealed that after single doses of 5-AS 1 g and SZ 2 g between 0.01% and 0.75% could be recovered in collected bile (85–500 ml/day) as total AS (traces of free 5-AS, and acetylated and glucuronidated 5-AS), indicating some enterohepatic circulation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542120
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  • 49
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of canrenone after oral administration of spironolactone and intravenous injection of canrenoate-K in healthy man (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 449-453 
    Details
    ISSN: 1432-1041
    Schlagwort(e): canrenone ; pharmacokinetics ; plasma level ; bioavailability ; urinary excretion ; spironolactone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five healthy male volunteers received canrenoate-K 200 mg (Sincomen® pro injectione) by intravenous injection and one week later spironolactone 200 mg (Sincomen®-100) orally. Plasma levels and urinary excretion of unchanged canrenone were determined up to 24 h by a specific HPLC method. Following intravenous administration, the maximum plasma level of 2066±876 ng/ml was found after 29±15 min and thereafter the concentration declined with a half-life of 3.7±1.2 h. Total clearance was 4.2±1.7 ml/min·kg. After oral ingestion, the maximum concentration of 177±33 ng/ml was observed at 4.4±0.9 h. The absolute bioavailability of canrenone was 25±9%. Within 24 h, respectively 0.4 and 0.6 mg, canrenone were excreted by the kidney after intravenous and oral administration. The half-life of elimination was 4.9±1.8 h (i.v.) and 3.9±1.2 h (p.o.).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542109
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  • 50
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of methadone in methadone maintenance treatment: Characterization of therapeutic failures (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 497-501 
    Details
    ISSN: 1432-1041
    Schlagwort(e): methadone ; pharmacokinetics ; steady state ; addiction rehabilitation ; therapeutic failure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Deuterated methadone (M-d3) and GC-MS analysis were used to study the steady state pharmacokinetics of methadone (M) in eight patients reported as therapeutic failures in a methadone maintenance treatment programme. The patients were compared to an unselected group of 12 patients stabilized on M for 25 days. During one dosage interval a pulse dose of M-d3 was administered intravenously instead of the oral M-dose (M-d0). The pharmacokinetic parameters, half-life in the β-phase (t1/2β), volume of distribution during the postdistributive phase (Vdβ) and during steady state (Vdss) were determined as well as the body (ClS) and renal (ClR) clearances of M. Pronounced differences in Vdβ and Vdss were found between the two groups. The therapeutic failures had a smaller Vdβ and Vdss 3.09±0.96 l/kg and 2.74±0.96 l/kg vs 4.56±1.00 l/kg and 4.20±0.78 l/kg in the control group. The differences were due to changes between the groups in the volume of the central compartment. Differences between the groups were also found in t1/2β — 24.5±2.6 h in the therapeutic failures and 34.0±7.0 h (p〈0.001) in the comparison group. However, the change in t1/2β was probably a consequence of the change in Vdβ, as the body clearance of M was similar in the two groups — 104±36 ml/min vs 111±36 ml/min. The smaller volume of distribution could lead to unacceptably high fluctuation of M in the central compartment, and withdrawal symptoms during the latter part of the dosage interval. The appropriate treatment of this subgroup of patients on methadone treatment is not to increase the dose but to shorten the dosage interval. Alternatively, a longer-acting opiate, such as 1-α-acetylmethadol (LAAM), may be used.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542117
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  • 51
    Digitale Medien
    Digitale Medien
    Pharmacodynamic and pharmacokinetic study of oral and intravenous penbutolol (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 529-534 
    Details
    ISSN: 1432-1041
    Schlagwort(e): penbutolol ; pharmacokinetics ; blood pressure effect ; heart rate effect ; dose response relationship ; tolerance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The present study was done to establish the dose-response relationships for effects on heart rate and systolic and diastolic blood pressure, tolerance and plasma disappearance kinetics after large intravenous and oral doses of penbutolol. Twelve healthy volunteers were randomly allocated to receive penbutolol (n=8) or placebo (n=4) in this single blind, placebo-controlled investigation. The degree of beta-blockade was measured by standarized exercise tests at work loads selected to produce a heart rate of 150/min without treatment. Penbutolol was given as single i.v. doses of 3, 6 and 12 mg and as 40, 80 and 120 mg once daily for one week, measurements being made 2 and 24 h after the last dose. Penbutolol i.v. did not influence the resting heart rate but it did reduce resting systolic blood pressure in a non-dose dependent manner. Exercise heart rate and systolic pressure were lowered by all the intravenous doses. All oral doses of penbutolol lowered exercise heart rate and systolic blood pressure to the same extent. The reductions in exercise tachycardia was still present after 24 h. After i.v. administration t1/2 was approximately 1.2 h and the volume of distribution was 32–42 l. All doses were well tolerated.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542123
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  • 52
    Digitale Medien
    Digitale Medien
    Assessment of drug metabolism in hepatic disease: Comparison of plasma kinetics of oral cyclobarbital and the intravenous aminopyrine breath test (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 95-101 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cyclobarbital ; aminopyrine ; liver disease ; 14CO2 breath test ; barbiturate ; pharmacokinetics ; hepatic drug metabolism ; cirrhosis ; alcoholic liver disease ; viral hepatitis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The exhalation of 14CO2 derived from an i.v. tracer dose of [dimethylamine-14C]aminopyrine has been investigated in normal controls and patients. They subsequently ingested 200 mg cyclobarbital calcium in the evening and the decline in the plasma drug level over the following 2 days was measured by thin-layer chromatography. The peak specific activity of exhaled 14CO2 occurred 0.5–2 h after 14C-aminopyrine injection in the absence of liver disease and in non-cirrhotic liver disorders. It was delayed in certain patients with cirrhosis. Compared to 8 medically healthy subjects, 10 patients with acute viral hepatitis, 8 with cirrhosis and 10 with fatty liver exhibited a significantly increased half-life of 14CO2 exhalation. Normal mean values were found in 12 patients with non-cirrhotic alcoholic liver disease and in 14 patients with non-hepatic diseases. The cyclobarbital (CB) half-life was prolonged and the clearance reduced in patients with viral hepatitis, cirrhosis, or alcoholic liver damage as compared to data from 17 control subjects. Due to a larger apparent volume of distribution, patients with fatty liver disease had an increased CB half-life, although its clearance was normal. A close negative correlation was detected between the clearance and the logarithm of the CB level measured 36 h after drug ingestion. The oral CB test evaluated from a single blood sample taken about 36 h after drug administration appears to be a useful indicator of human drug metabolising capacity. Discrimination between patients with and without disordered liver function was similar in the two drug elimination tests.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00546715
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  • 53
    Digitale Medien
    Digitale Medien
    Circadian profiles of blood glucose and plasma free insulin during treatment with Semisynthetic and Biosynthetic human insulin, and comparison with conventional monocomponent preparations (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 767-771 
    Details
    ISSN: 1432-1041
    Schlagwort(e): human insulin ; diabetes control ; blood glucose ; free insulin ; biosynthetic insulin ; semisynthetic insulin ; monocomponent insulin ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Sixteen hospitalized insulin requiring diabetics treated with a single daily subcutaneous injection were randomly allocated either to a mixture of porcine Actrapid+Lente MC or a mixture of Regular+NPH—Biosynthetic human insulin (Study 1). In Study 2, 10 patients receiving two daily insulin injections were treated at random with either porcine Actrapid+Monotard, or Actrapid+Monotard—Semisynthetic human insulin or Regular+NPH—Biosynthetic human insulin. Once an optimal insulin regimen was obtained, circadian blood glucose and plasma free insulin profiles (7–9 time points) were determined with the two (Study 1) or three (Study 2) insulin preparations, keeping the doses of insulin constant. In Study 1 no significant difference in blood glucose (BG) or plasma free insulin (FIRI) profiles was observed. The mean daily blood glucose, the mean amplitude of glycaemic excursions (MAGE), the index of blood glucose control (M-value of Schlichtkrull), as well as the post-breakfast increases in blood glucose and mean free IRI, were similar with both types of insulin. In Study 2, BG and FIRI profiles were also similar, except for a significantly lower (p〈0.02) BG at 8.30 p.m. with both human insulins. No significant differences were found in free IRI at that time. Mean BG, M index, MAGE and mean FIRI were similar but the postbreakfast increase was significantly smaller with SHI. In conclusion, the pharmacokinetics of animal monocomponent, semisynthetic and biosynthetic human insulin appear similar, but evening BG control was better with both types of human insulins given twice daily.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542517
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  • 54
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of midazolam in the aged (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 381-388 
    Details
    ISSN: 1432-1041
    Schlagwort(e): midazolam ; hypnotic drug ; benzodiazepine ; pharmacokinetics ; aged patients
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of midazolam, an imidazo-benzodiazepine derivative, have been studied in 13 subjects over the age of 60 years who received the drug intravenously (0.07 mg kg−1) as an induction agent for endoscopy. Two to three days later, 6 of these subjects received 5 mg of midazolam intramuscularly, and another 6 of the subjects received 10 mg of the drug orally. The plasma concentration-time curves were again studied pharmacokinetically. After intravenous dosing, the mean (± SD) elimination half-life (2.14±1.24 h) showed a statistically significant trend to increase with age in the subjects older than 60 years. While the mean (± SD) clearance value (0.30±0.19 l kg−1h−1) tended to fall with age in the elderly subjects, this trend was not statistically significant. Apparent volume of distribution did not appear to be related to advancing age beyond 60 years, and this parameter (mean ± SD) did not differ to a statistically significant extent between the aged subjects (0.77±0.47 l kg−1) and the young subjects studied previously (1.09±0.58 l kg−1). Atropine premedication did not appear to alter the dispositional parameters of the intravenously administered drug. Intramuscularly administered midazolam was absorbed rapidly. Bioavailability appeared incomplete (F=0.59±0.15, mean ± SD), possibly due to saturable elimination of the drug at the higher plasma levels which were obtained after intravenous midazolam. Oral bioavailability, relative to intravenous, was 0.34±0.17, (mean ± SD), with an appreciable but variable lag time (0.74±0.40 h, mean ± SD). Orally, in the dose used, the drug was an inefficient hypnotic with four of the six subjects failing to attain the plasma drug level of 44–50 µg l−1, which appeared to be the approximate threshold for sleep. It is impossible to know whether this failure represents an age related effect on drug absorption, or is a consequence of the upper alimentary tract abnormalities for which the endoscopies were done.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00548771
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  • 55
    Digitale Medien
    Digitale Medien
    Single and multiple dose kinetics of clobazam, and clinical effects during multiple dosage (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 499-503 
    Details
    ISSN: 1432-1041
    Schlagwort(e): benzodiazepines ; clobazam ; desmethylclobazam ; pharmacokinetics ; sedation ; accumulation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Sixteen healthy volunteers, aged 19 to 62 years, took a single 20-mg oral dose of clobazam and the serum concentrations of clobazam and desmethylclobazam were measured for the following 7 days. The mean kinetic variables for clobazam were: volume of distribution 1.31/kg, elimination half-life 24 h, total clearance 0.47 ml/min/kg. 13 of the volunteers then took clobazam 5 mg twice daily for 22 consecutive days. Serum concentrations were measured during and after this period. Both clobazam and desmethylclobazam showed slow and extensive accumulation, their steady-state kinetics being entirely consistent with those observed after single doses. Elimination of both compounds after termination of treatment was equally slow. Clinical self-rating of morning sedation indicated a significant increase over baseline in subjective perception of sedation during the treatment period, and this effect persisted into the washout period. However, sedation did not increase in parallel with accumulating levels of clobazam and desmethylclobazam, probably due to functional adaptation or tolerance.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542148
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  • 56
    Digitale Medien
    Digitale Medien
    Bioequivalence studies in humans of indomethacin capsules marketed in India (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 261-264 
    Details
    ISSN: 1432-1041
    Schlagwort(e): indomethacin capsules ; bioequivalence ; volunteers ; pharmacokinetics ; statistical significance ; bioavailability ; comparative bioequivalence
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Two, separate 6×6 Latin square cross-over bioequivalence studies were performed in adult male volunteers using 10 different indomethacin capsule preparations marketed in India together with the pure drug powder as the standard. The products were evaluated with respect to plasma level at various times up to 8 h following administration of a 50 mg (2 × 25 mg) dose. Plasma samples were analysed by a fluorimetric method. Various pharmacokinetic parameters were calculated according to a two compartment model. Statistical evaluation of the data employed analysis of variance for a cross-over design (ANOVA) and Duncan's multiple range test to ascertain the significance of differences between the products. Of the 10 products studied, two were found to be bioinequivalent.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00630296
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  • 57
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of cefoxitin administered by i.v. infusion to patients with a pleural effusion (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 389-392 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cefoxitin ; beta-lactam antibiotics ; pharmacokinetics ; serum concentration ; pleural fluid concentration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of cefoxitin was studied in 6 healthy volunteers and in 5 patients with a pleural effusion after administration of a single dose of 30 mg/kg i.v. infusion. The serum and pleural fluid concentrations of cefoxitin were determined microbiologically. The elimination half-life of the antibiotic from pleural fluid in all cases was 2–3fold longer than from serum, which shows a difference between the kinetic elimination processes of the antibiotic from the two fluids. The slow elimination of cefoxitin from pleural fluid facilitates its accumulation in this compartment during a multiple dosage regimen.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00548772
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  • 58
    Digitale Medien
    Digitale Medien
    Initiation and maintenance of beta-blockade with intravenous oxprenolol (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 7-14 
    Details
    ISSN: 1432-1041
    Schlagwort(e): oxprenolol ; coronary heart disease ; normals ; pharmacodynamics ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma concentration profile of oxprenolol after intravenous bolus injection, during intravenous infusion and following sustained oral administration was studied in a total of 106 patients with coronary heart disease. Speed of onset of pharmacodynamic activity, as measured by suppression of isoprenaline tachycardia, was discernible within a few seconds of central injection and complete within 5 min in all patients; variability in response was small. Following both i.v. bolus and intravenous infusion, plasma oxprenolol concentrations showed considerable between patient variability The plasma concentration/time profile observed in 16 patients following single intravenous oxprenolol bolus therapy was substantially higher, particularly during the early distribution phase, than observed and predicted volunteer data. Higher plasma oxprenolol concentrations were also attained during the more extended time sampling of the infusion studies; these findings would be compatible with reduced oxprenolol clearance in patients with ischaemic heart disease. During chronic oral therapy there was a many-fold between-subject variability in plasma concentration achieved following a given ingested dose. Correlation of antagonism of exercise tachycardia inhibition with plasma oxprenolol concentration in 15 male volunteers demonstrated near complete blockade of exercise stimulation of chronotropic beta-adrenoceptors at an average plasma oxprenolol concentration of 150 ng/ml. In coronary heart disease, such plasma concentrations can most conveniently be achieved by a 4 mg oxprenolol intravenous bolus with simultaneous infusion of 0.05 mg/kg/h; however, these studies provide sufficient information to allow alternative regimens to be derived should lesser plasma concentrations be considered desirable.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613920
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  • 59
    Digitale Medien
    Digitale Medien
    Disposition kinetics of metronidazole in children (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 113-119 
    Details
    ISSN: 1432-1041
    Schlagwort(e): metronidazole ; trichomonas vaginitis ; children ; pharmacokinetics ; serum and saliva concentrations ; therapeutic dosage schedule ; anaerobic infection
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of metronidazole was studied in 20 paediatric patients aged 6 weeks and 4 to 14 years, who had trichomonal vaginitis or an anaerobic bacterial infection. The dosage of metronidazole was about 10 or 20 mg/kg b.i.d. orally. The serum concentrations found in children and the corresponding calculated kinetic parameters were similar to those in adults after intake of an equal, weight-related dose. Metronidazole shows rapid diffusion into the saliva with a concentration ratio of about 1.0. This can provide the basis for an efficient non-invasive method of drug monitoring.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613937
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  • 60
    Digitale Medien
    Digitale Medien
    Acute antihypertensive effect and pharmacokinetics of a tablet preparation of nifedipine (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 145-150 
    Details
    ISSN: 1432-1041
    Schlagwort(e): nifedipine ; hypertension ; pharmacokinetics ; tablet formulation ; dose-response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A tablet formulation of nifedipine was given to 8 hospitalized hypertensive men, W.H.O. stage I or II, mean age 45 years. After an initial placebo test, nifedipine 20, 40 or 60 mg was given in random order at 72-h intervals, in a single administration crossover study. The placebo and the active drug were given at 8 a.m. Blood pressure and heart rate were measured twice by the same observer, every 20 min from 7 to 8 a.m., and then hourly until 8 p.m., first in recumbency and again after 1 min of standing upright. Plasma nifedipine was assayed in samples taken hourly from 8 a.m. to noon, every 2 h from noon to 8 p.m., and 24 and 48 h after drug administration. All 3 doses significantly lowered blood pressure; the fall during recumbency was significantly larger (−18%) and lasted longer (12 h) after 60 mg than after 20 mg (−11% and 7 h). All 3 doses caused a similar increase in heart rate (+29 to +38%), which reached its maximum after 2 h and lasted for 5 h. The maximum plasma concentration and the area under the plasma concentration — time curve were dose-dependent despite large inter-subject variation. Absorption, bioavailability and elimination were linear between the 20 and 60 mg doses. Plasma nifedipine levels were strongly correlated with the concomitant decrease in mean arterial blood pressure (r=0.61,p〈0.001). Four patients experienced mild side effects (headaches, flushes, drowsiness or weakness). This tablet form of nifedipine has a potent antihypertensive action which lasts longer than that of the capsule presentation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613808
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  • 61
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of Sobrerol in chronic bronchitis (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 209-215 
    Details
    ISSN: 1432-1041
    Schlagwort(e): sobrerol ; mucus liquefaction ; pharmacokinetics ; bronchial mucus level ; mass fragmentography ; metabolites
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic profile of Sobrerol, a mucolytic drug, has been studied in patients with acute exacerbations of chronic bronchitis and dense sputum. In addition to measurement of serum and urine levels, the concentration in bronchial mucus was also examined, and their correlation was calculated. Mass fragmentographic analysis was used to assay free sobrerol and its principal urinary metabolites hydrated carvone and glucuronidated sobrerol. After the doses and administration routes used, there appeared to be accumulation of sobrerol in bronchial mucus. This is a feature of great interest and value for a drug which has the specific action of liquefying mucus.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00613819
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  • 62
    Digitale Medien
    Digitale Medien
    Acetaminophen accumulation in pediatric patients after repeated therapeutic doses (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 57-59 
    Details
    ISSN: 1432-1041
    Schlagwort(e): acetaminophen ; pediatric patients ; fever therapy ; accumulation ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Acetaminophen serum concentrations were studied in 21 infants and children with fever. The maximum serum concentrations ranged from 9.96 to 19.6 µg/ml after a single dose of 12–14 mg/kg and 13.9 to 40.1 µg/ml after a single dose of 22–27 mg/kg. Ten patients were restudied at steadystate after repeat doses had been given every 4 or 8 h for 1 to 3 days. Total area under the acetaminophen serum concentration-time curve normalized for dose averaged 0.181 (ml/min/kg)−1 after the first dose and 0.202 (ml/min/kg)−1 at steady-state (p〈0.05). Five patients showed a 13 to 44% increase in the AUC; one had a 10% decrease in the AUC; and four had less than 6% change in the AUC. There was no evidence of hepatotoxicity. These data suggest that acetaminophen may accumulate after repeated therapeutic doses in children with fever.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00553155
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  • 63
    Digitale Medien
    Digitale Medien
    Delayed elimination of triamterene and its active metabolite in chronic renal failure (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 453-456 
    Details
    ISSN: 1432-1041
    Schlagwort(e): triameteren ; renal failure ; hydroxytriamterene sulphate ; pharmacokinetics ; plasma protein binding ; urinary excretion ; renal tubular secretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of triamterene and its active phase II metabolite were studied in 32 patients with various degrees of impaired renal function; the creatinine clearances ranged from 135 to 10 ml/min. The area under the plasma concentration-time curves (AUC) for triamterene were not influenced by kidney function, but the AUCs for the effective metabolite OH-TA-ester were significantly elevated in renal failure, indicating accumulation of the metabolite. Urinary recovery of triamterene and its metabolite over a 48 h collection period was significantly reduced in renal failure. This is considered to be due to delayed urinary excretion, corresponding to reduced renal clearance. The renal clearance of the native drug exceeded that of the metabolite, because of their different protein binding, 55% for triamterene and 91% for the metabolite. The latter is eliminated almost exclusively via tubular secretion and extrarenal elimination is less important. Administration of this antikaliuretic is therefore considered hazardous in patients with impaired kidney function.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609885
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  • 64
    Digitale Medien
    Digitale Medien
    Relationship between pharmacokinetic and pharmacodynamic behaviour of bufuralol and its metabolite Ro 3-7410 in hypertensive patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 479-484 
    Details
    ISSN: 1432-1041
    Schlagwort(e): bufuralol ; hypotensive therapy ; pharmacokinetics ; hypertension ; 1-hydroxybufuralol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The relationship between the plasma concentrations of bufuralol and its major hydroxymetabolite (Ro 3-7410) and β-blocking activity was studied in 10 patients with uncomplicated essential hypertension. Blood samples and haemodynamic data were obtained during rest and after a single-level exercise test on a bicycle cycloergometer, prior to and up to 32 h after administration of a single oral dose of bufuralol 30 mg. Bufuralol was rapidly absorbed, following a first-order process with a lag time. The calculated maximal plasma concentration ranged from 44.6 to 200.3 ng/ml. The half-life of bufuralol was 2.75±1.15 h (mean±SD). Up to 50% of the parent drug was transformed into Ro 3-7410, which showed less interpatient variability in concentration and a fairly constant half-life, which was three times longer than that of the parent drug. In general, the heart rate (HR) was slightly decreased, although 2/10 patients showed an initial increase. The resting HR returned to its pre-treatment level within 6 h, the exercise HR took up to 32 h to return to the pre-treatment level. The drug reduced both resting and exercise blood pressure (BP). The former was reduced from 153.0±14.2/93.5±8.5 to 134.5±14.0/77.0±6.8 mmHg (systolic/diastolic BP; mean±SD) with 6 h after treatment. Similarly, the exercise BP was reduced from 199.0±15.2/98.5±8.8 to 171.0±9.9/88.5±8.5 mmHg at the 6th h post-dosing. The BP values had not returned to their pre-treatment levels even 32 h after treatment. Thus, bufuralol and its metabolite Ro 3-7410 induced a long-lasting antihypertensive effect and inhibited the cardio-acceleratory effect of exercise, and there was a good correlation between the pharmacokinetic and pharmacodynamic behaviour of the drug.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609890
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  • 65
    Digitale Medien
    Digitale Medien
    Pharmacokinetics in man of a new antiarrhythmic drug, cibenzoline (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 509-515 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cibenzoline ; pharmacokinetics ; bioavailability ; urinary excretion ; antiarrhythmic drug ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of cibenzoline (UP 339.01), a new antiarrhythmic drug, was studied after i.v. and oral administration to 5 healthy subjects. Cibenzoline levels in plasma and urine cibenzoline were measured by a GLC method. After i.v. administration, the total clearance was 826 ml · min−1. The fraction of cibenzoline excreted unchanged in the urine was 0.602 and it was correlated with the creatinine clearance. After i.v. and oral administration, the renal clearances were 499 ml · min−1 and 439 ml · min−1, and the half-lives were 4 h 01 min and 3 h 24 min, respectively. The differences were not significant. Availability by the oral route was 0.92, the maximum plasma concentration being observed at 1 h 36 min. The results were compared with those for other antiarrhythmic drugs.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00609894
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  • 66
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of diltiazem in severe renal failure (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 635-638 
    Details
    ISSN: 1432-1041
    Schlagwort(e): calcium antagonist ; diltiazem ; renal failure ; pharmacokinetics ; desacetyldiltiazem ; metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The acute effects of a single dose of diltiazem (Tildiem®), a calcium antagonist, were studied in 9 patients with severely impaired renal function (GFR between 0.03 and 0.87 ml/s/1.73 m2). Control measurements were made of inulin and PAH clearance, creatinine, blood pressure, heart rate and ECG. Following administration of diltiazem 120 mg, 7 blood samples were collected in the first 12 h and after 24 h, 32 h, 48 h; urine was collected for the first 12 h, 12–24 h and 24–48 h, and blood pressure, heart rate and ECG were recorded after 6 h. Diltiazem and its main metabolite, desacetyldiltiazem, had a pharmacokinetic profile similar to that in patients with normal renal function (peak plasma concentration, half-life and urinary excretion). Diltiazem is normally eliminated in the urine to a small extent, because it is metabolized, and this also applies to desacetyldiltiazem, which is probably further metabolized.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542213
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  • 67
    Digitale Medien
    Digitale Medien
    Comparative pharmacokinetic profiles of metoprolol and chlorthalidone administered alone or in combination to healthy volunteers (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 655-660 
    Details
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; chlorthalidone ; co-administration ; pharmacokinetics ; healthy subjects ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A potential pharmacokinetic interaction between the beta-blocking drug, metoprolol, and the diuretic, chlorthalidone, has been investigated in three single or multiple dose studies in healthy volunteers. The pharmacokinetic profile of metoprolol 100 mg was not affected by pretreatment with or co-administration of chlorthalidone 25 mg twice daily. Similarly, the pre-dosing steady-state level of chlorthalidone during chronic treatment and its blood level profile after a single 25 mg dose were not affected by metoprolol. The bioavailabilities of the 2 drugs administered in combination were identical to those observed when each drug was administered alone. These studies demonstrate that there is no pharmacokinetic interaction between metoprolol and chlorthalidone when doses of 100 and 25 mg, respectively, are co-administered twice daily.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542217
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  • 68
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of canrenone and metabolites after base hydrolysis following single and multiple dose oral administration of spironolactone (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 441-446 
    Details
    ISSN: 1432-1041
    Schlagwort(e): spironolactone ; canrenone ; metabolites ; pharmacokinetics ; single/multiple oral doses ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of canrenone and ‘total metabolites’ after base hydrolysis was studied in eight young volunteers following single and multiple dose oral administration of spironolactone. The plasma levels of canrenone and ‘total metabolites’ were fitted to a two-compartment open model with a first-order absorption process. From our eight normal subjects studied, the harmonic mean of the distributive half-life (t1/2α) of canrenone was found to be 1.66 h, and the harmonic mean of the terminal elimination half-life (t1/2β) to be 22.6 h. Harmonic means of the distributive and elimination half-lives of ‘total metabolites’ after base hydrolysis were 2.48 h and 28.8 h respectively. The accumulation ratio of canrenone was 2.53, whereas that of ‘total metabolites’ was 1.89. Despite the fact that spironolactone has been shown to induce hepatic metabolism of other drugs, no evidence of autoinduction was noted in the present study, as plasma levels of canrenone and ‘total metabolites’ were found to obey a linear two-compartment model with reproducible absorption and disposition after single and multiple doses.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00549592
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  • 69
    Digitale Medien
    Digitale Medien
    A “once a day administration” sustained-release theophylline formulation: Disposition and pharmacokinetics (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 325-328 
    Details
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; sustained release ; pharmacokinetics ; chronic administration ; healthy volunteers ; plasma levels ; GCMS assay ; stable isotope technique
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of a new sustained-release preparation of theophylline (Dilatrane à Action Prolongée capsules filled with homogenous microgranules) has been after its studied administration to 7 healthy volunteers at 8 p.m. in order to achieve therapeutic levels at night and in the morning. In separate trials the test dose of 500 or 600 mg was administered for 7 days, once daily at 8 p.m. Plasma theophylline levels were measured by capillary gas chromatography with a mass specific detector after pentylation, using internal standards labelled with stable isotopes (15N-1,3 and 13C-2 theophylline). The new sustained-release preparation showed a monophasic regular absorption phase with very low interindividual variability. After administration, the plasma level stayed within 80% of the peak levels for 8.5±1.5 h. There was a good correlation between the dose and the steady state plasma level (r=0.9587; p〈0.05). This preparation can be chronically administered once daily day at 8 p.m. in order to achieve a therapeutic level during the night and the morning, and to provide sufficient protection during the nycterohemeral period, with a once dose a day schedule.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542169
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  • 70
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of a fixed combination of sotalol and hydrochlorothiazide in hypertensive patients with moderate renal insufficiency (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 361-362 
    Details
    ISSN: 1432-1041
    Schlagwort(e): sotalol ; hydrochlorothiazide ; pharmacokinetics ; moderate renal failure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Decreased elimination of a combined formulation of Sotalol (160 mg) and hydrochlorothiazide (25 mg) was found in patients with moderate renal insufficiency. Very slight accumulation of sotalol and hydrochlorothiazide was observed, so it appears unnecessary to reduce the dosage in patients with a creatinine clearance of 30 ml/min or more.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542176
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  • 71
    Digitale Medien
    Digitale Medien
    The pharmacokinetics of a new radiosensitiser, Ro 03-8799 in humans (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 483-489 
    Details
    ISSN: 1432-1041
    Schlagwort(e): radiosensitiser ; pharmacokinetics ; healthy volunteers ; tumour patients ; Ro 03-8799
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A new hypoxic cell radiosensitiser, Ro 03-8799 has been administered intravenously to human volunteers and its kinetic parameters derived from plasma and urine data. Good penetration of drug into tumour tissue is found, consistent with its large volume of distribution. The plasma clearance of this compound is rapid due to high metabolic and renal clearances. These parameters combine to produce an elimination half-life of 5.6 h, approximately half that of misonidazole, a well studied radiosensitiser. It is hoped that this decrease in total body exposure will also reduce the cumulative toxicity seen when misonidazole is administered repeatedly.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00549599
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  • 72
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of digoxin in pregnancy (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 117-121 
    Details
    ISSN: 1432-1041
    Schlagwort(e): serum digoxin ; pregnancy ; digoxin-renal-clearance ; creatinine-clearance ; digoxin-elimination ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Digoxin-renal-clearance, creatinine-clearance, 24-h urine elimination of digoxin and serum digoxin were studied in 15 patients in the third trimester of pregnancy and 6 to 12 weeks post-partum. There was significant fall post-partum in the first three. There was also a significant fall post-partum in serum digoxin levels. This finding was unexpected, but may be due to heightened absorption exceeding increased elimination because of the physiological status in pregnancy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00544027
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  • 73
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of the new aldosterone antagonist, spirorenone, in healthy volunteers after single and repeated daily doses (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 231-236 
    Details
    ISSN: 1432-1041
    Schlagwort(e): spirorenone ; pharmacokinetics ; aldosterone antagonist ; active metabolite ; absorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma concentrations of spirorenone in two groups of male volunteers have been determined after single and 14 daily doses of spirorenone 10 and 40 mg. Independent of the dose and pretreatment, spirorenone was absorbed with a half-life of 20–30 min, achieving maximum concentrations of about 100 ng/ml (10 mg) and 260 ng/ml (40 mg) after 1–2 h. Disposition of the parent drug was biphasic with half-lives of 50–60 min (distribution) and 5–6 h (elimination). Neither significant accumulation nor enzyme induction were observed after prolonged treatment. In one test subject given spirorenone 40 mg, the concentration of an active metabolite, 1,2-dihydrospirorenone, was measured. This compound accumulated considerably after multiple dosing and the area under the plasma concentration-time curve increased from 16 to 52% relative to that of spirorenone itself.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00543796
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  • 74
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of aspirin and salicylate in elderly subjects and in patients with alcoholic liver disease (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 253-261 
    Details
    ISSN: 1432-1041
    Schlagwort(e): aspirin ; pharmacokinetics ; salicylate ; alcoholic liver disease ; young and elderly volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma aspirin, salicylate and salicyluric acid concentrations were monitored in young, elderly and alcoholic subjects after ingestion of a single 1.2 g dose of soluble aspirin. The plasma aspirin, salicylate and unbound salicylate concentration-time profiles varied considerably between individual subjects. Most of the pharmacokinetic parameters derived from these profiles were not significantly different between young subjects, elderly subjects and subjects with alcoholic liver disease. Individual plasma albumin concentrations provided a better index of the unbound plasma salicylate clearances and salicylate plasma protein binding than the age of the subject or the presence of alcoholic liver disease. Highest unbound plasma salicylate concentrations were found in subjects with the lowest plasma albumin concentrations.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00543800
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  • 75
    Digitale Medien
    Digitale Medien
    Pharmacokinetics and bioavailability of three dyphylline preparations (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 281-283 
    Details
    ISSN: 1432-1041
    Schlagwort(e): dyphylline ; pharmacokinetics ; bioavailability ; drug levels
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and bioavailability of 3 oral dyphylline preparations, solution (S), regular (R) and sustained release (SR), were studied in 8 healthy subjects (mean age 25 years). A single dose of each preparation, 20 mg·kg−1, was given at one week intervals and multiple serum samples obtained over 24 h. Drug levels were measured by high performance liquid chromatography. No adverse effects were found. The dyphylline half-life for the solution was 2.16±0.18 h and for the tablet 2.59±0.56 h. The mean clearance rate for S was 13.6±1.7 h−1 and volume of distribution 43.0±3.91. Peak concentration (Cmax, µg·ml−1), time of peak (Tmax, h), area under the curve (AUC, µg·ml−1·h) and relative bioavailability (RB, %), were determined for three preparations: The data confirm the short half-life of dyphylline, demonstrate a lack of toxicity for the 20 mg·kg−1 dose and establish bioequivalence for the products studied.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00543805
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  • 76
    Digitale Medien
    Digitale Medien
    The influence of uremia on the accessibility of phosphomycin into interstitial tissue fluid (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 333-338 
    Details
    ISSN: 1432-1041
    Schlagwort(e): phosphomycin ; pharmacokinetics ; impaired renal function ; “skin blister” ; interstitial fluid
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The entry and persistence of phosphomycin in interstitial tissue fluid (ITF) were studied in 9 patients with normal renal function and 8 patients with varying degrees of renal impairment, all of whom received a single i.v. dose of 30 mg/kg. ITF was obtained from skin blisters produced by suction. The antibiotic followed a two-compartment open kinetic model. In patients with normal renal function, phosphomycin is incorporated rapidly into the ITF reaching a level of 60.4 µg/ml 60 min after administration. There was no statistically significant difference between the elimination rates from serum and ITF. The serum half-life of the slow disposition phase was 1.75 h in patients with normal renal function. There was a linear correlation between the elimination half-life of phosphomycin in serum and ITF in subjects with differing degrees of renal impairment.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01037944
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  • 77
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of fenclofenac in children with juvenile rheumatoid arthritis (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 381-388 
    Details
    ISSN: 1432-1041
    Schlagwort(e): fenclofenac ; pharmacokinetics ; juvenile rheumatoid arthritis ; side effects ; synovial fluid drug level
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Twenty eight children (age range 3–17 years) with juvenile rheumatoid arthritis (JRA) received fenclofenac 10–25 mg/kg body weight daily on an open basis. Pharmacokinetic analysis was undertaken on plasma fenclofenac levels measured during the first 3 weeks of treatment. The peak concentration after the first dose was achieved in 2–8 h in non-fasting subjects and was linearly related to dose. The plasma level then decayed biexponentially, as in adults, the initial distribution phase extending to about 12 h after dosing. After treatment for 18 days, blood samples were taken during the 96 h following the last dose of the drug to define the steady state elimination profile. The elimination half-life was 25.4±7.9 h (n=17) and did not appear to be dependent on the daily dosage. A therapeutic drug concentration of ≥100 µg/ml emerged from subjective and objective estimates of the response to treatment and measurement of steady state fenclofenac concentration. Treatment response could be more accurately predicted with the aid of drug concentrations than from dosage alone, although the dose and the steady state drug concentration were positively and linearly correlated (r=0.61,p〈0.01). Of 16 children receiving doses in excess of 20 mg/kg/day, 3 experienced dose-related adverse effects, increased serum transaminase activity, vertigo and dyspnoea.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01037952
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  • 78
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of cefoxitin during haemofiltration (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 395-398 
    Details
    ISSN: 1432-1041
    Schlagwort(e): haemofiltration ; cefoxitin ; pharmacokinetics ; renal failure ; beta-lactam-antibiotics ; haemodialysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of cefoxitin was studied in patients with renal impairment during haemofiltration and in the intervening periods after administration of 30 and 15 mg/kg of the drug, respectively. Different pharmacokinetic patterns were established during haemofiltration and in the interim period, with average elimination half-lives of 11.85±4.3 and 3.41±0.6 h, respectively. The average fraction of the cefoxitin dose eliminated in haemofiltration was 0.62±0.11, more than that established in haemodialysis. In patients with terminal renal impairment undergoing haemofiltration every 48 h, a dose of 15 or 30 mg/kg is recommended at the start and at the end of each haemofiltration session.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01037954
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  • 79
    Digitale Medien
    Digitale Medien
    Volume of distribution terms for a drug (ceftriaxone) exhibiting concentration-dependent protein binding II. Physiological significance (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 407-412 
    Details
    ISSN: 1432-1041
    Schlagwort(e): ceftriaxone ; pharmacokinetics ; concentration-dependent binding ; volume of distribution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Guidelines presented previously for the analysis of plasma concentration versus time data for a drug exhibiting concentration-dependent plasma protein binding were successfully applied to the distributional parameters of a new cephalosporin, ceftriaxone. This approach provided several striking observations when the pharmacokinetics of ceftriaxone in a healthy and uremic population were re-examined. First, the parameter $$\bar f_P $$ converted the apparent dose-dependent distributional terms of ceftriaxone into a function of the concentration-dependent plasma protein binding. Second, a strong correlation between the term V SS U and the reciprocal of $$\bar f_P $$ was established within each of the two populations. While this $$\bar f_P $$ term accounted for the variability within the respective populations due to ceftriaxone-albumin binding differences, it did not account for all of the distributional differences between the two populations. The present analysis revealed that the altered physiologic state of uremia (larger plasma volumes and interstitial to intravascular albumin ratios), in addition to differences in plasma protein binding, dictated the distribution of ceftriaxone in healthy and uremic subjects. Furthermore, the binding-disposition model which accounts for the presence of plasma proteins outside the vascular space, was established to be appropriate in describing the distribution of ceftriaxone.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01037956
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  • 80
    Digitale Medien
    Digitale Medien
    Cefoxitin in newborn infants (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 507-509 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cefoxitin ; newborn infants ; bacterial infection ; pharmacokinetics ; cephalosporin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Fifteen patients less than 2 months old with bacterial infections caused by pathogens known or presumed to be sensitive to cefoxitin were studied. Cefoxitin was administered as an i.v. bolus injection over 15 min, every 8 h for 6 to 12 days, to a total daily dosage of 90 mg/kg. In 14 patients cefoxitin therapy resulted in eradication of the pathogen and in recovery from clinical signs of infection. Only one patient did not respond to cefoxitin therapy. No adverse clinical or haematological effects definitely caused by cefoxitin were observed. Plasma and urine samples collected after the first dose were assayed for cefoxitin by HPLC. Pharmacokinetic data indicated larger apparent volume of distribution (0.51/kg), a smaller plasma clearance (0.271/h/kg) and a longer half-life (1.43 h) than in adults. The plasma half-life was inversely correlated (p〈0.05) to the postnatal age of the patients. Cefoxitin may be safely used in infants with infections caused by susceptible pathogens.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542119
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  • 81
    Digitale Medien
    Digitale Medien
    Single and repeated dose kinetics of the hypnotic agent loprazolam in healthy volunteers (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 651-655 
    Details
    ISSN: 1432-1041
    Schlagwort(e): loprazolam ; pharmacokinetics ; repeated dose
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of loprazolam have been studied in eight healthy male volunteers after single and repeated 2 mg oral doses taken at night, for eight nights. The absorption and disposition of unchanged drug (HPLC-GC assay) and receptor active benzodiazepine-type materials (radioreceptor assay) were examined after the first and eighth dose. Maximum levels of approximately 10 ng ml−1 (range 3.6 to 15.5 ng ml−1) were reached within about 2.5 h after dosing. The post-peak levels declined in a single exponential fashion with an overall mean±SD half-life of 7.06±1.98 h and total areas under the curve ranging from 35.9 to 189.0 ng ml−1 h. There were no statistical differences between the values for the first and eighth doses. There was no evidence to suggest that significant accumulation of parent drug or receptor active benzodiazepine-type materials had occurred, and it is concluded that the kinetics of loprazolam would allow repeated daily doses of 2 mg.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542354
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  • 82
    Digitale Medien
    Digitale Medien
    Sex differences in the pharmacokinetics of salicylates (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 679-682 
    Details
    ISSN: 1432-1041
    Schlagwort(e): salicylic acid ; sex differences ; acetylsalicylic acid ; pharmacokinetics ; single and multiple doses ; elimination ; absorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of disposition of total and free salicylic acid (SA) in blood plasma was evaluated after single and multiple oral administration of acetylsalicylic acid (ASA) to healthy female and male volunteers. In both single and multiple dose studies significant sex differences were found in the plasma levels of SA, which were due, at least in part, to individual, sex-determined differences in the rate of absorption and elimination of SA; a slower absorption rate in men reduced the magnitude of the peak plasma levels of SA. The corresponding area under concentration-time curves were always significantly lower. The elimination rate of SA in men was increased in comparison with women. The higher plasma clearance in men resulted from the kinetics of absorption and elimination. The sex differences appear to be clinical significance, since men achieved lower plasma levels of SA than women after the same weight-adjusted dose of ASA.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542358
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  • 83
    Digitale Medien
    Digitale Medien
    Kinetics of oral fluphenazine disposition in humans by GC-MS (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 709-711 
    Details
    ISSN: 1432-1041
    Schlagwort(e): fluphenazine ; pharmacokinetics ; plasma concentrations ; intersubject differences
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The disposition of fluphenazine was investigated in six healthy volunteers following oral administration (5 mg). Using a sensitive and specific GC-MS procedure plasma fluphenazine concentrations were measured up until 32 h after drug administration. Peak plasma concentrations varied widely (range: 0.26–1.06 ng/ml) and were observed at 2.8±0.5 h following fluphenazine administration. The apparent terminal elimination half-life of fluphenazine was 33.1±8.1 h. The area under the plasma concentration-time curve differed widely between subjects (range: 7.1–28.6 ng/ml h) suggesting large interindividual differences in the extent of fluphenazine presystemic elimination.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542363
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  • 84
    Digitale Medien
    Digitale Medien
    Significance of acetylator phenotype in pharmacokinetics and adverse effects of procainamide (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 791-795 
    Details
    ISSN: 1432-1041
    Schlagwort(e): procainamide ; acetylator phenotype ; antinuclear antibodies ; N-acetylprocainamide ; antiarrhythmic drugs ; cardiac arrhythmias ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and development of antinuclear antibodies (ANAs) during procainamide (PA) therapy were studied in 35 patients with ventricular arrhythmias. Sixteen of the subjects were rapid and 19 were slow acetylators. Twenty-six of them (13 rapid and 13 slow acetylators) received PA therapy (2.4 g sustained-release PA·HCl daily in three doses) for at least 16 weeks. On maintenance therapy, rapid acetylators had insignificantly lower serum PA concentrations and slightly higher N-acetylprocainamide (NAPA) concentrations than slow acetylators. The unchanged PA fraction (PA/PA + NAPA) in the rapid acetylators was somewhat lower than in the slow acetylators. Rapid acetylators excreted more NAPA in urine than did slow acetylators (p〈0.05), whereas the difference in PA excretion was not significant. More than 80% of the given drug was excreted as PA and NAPA. Spontaneous or exercise-induced arrhythmias were recorded in 6 rapid and 8 slow acetylators. ANAs (titre at least 20) appeared in 6 rapid and 8 slow acetylators. The mean time until ANA development in rapid acetylators was only marginally longer than in slow acetylators. The results suggest that acetylation phenotyping is not of great significance in predicting the development of ANAs during PA therapy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542522
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  • 85
    Digitale Medien
    Digitale Medien
    Inter- and intra-subject variation in the first-pass elimination of highly cleared drugs during chronic dosing (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 47-53 
    Details
    ISSN: 1432-1041
    Schlagwort(e): verapamil ; first-pass metabolism ; pharmacokinetics ; interindividual variation ; intraindividual variation ; chronic administration ; deuterated verapamil
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of verapamil in five healthy volunteers were investigated on 4 occasions during chronic administration of deuterated verapamil. There was no statistically significant difference in oral clearance, terminal half-life, bioavailability, morning trough level and peak concentration or in the time of their occurrence on the four occasions. The plasma clearance, however, exhibited considerable inter- and intra-individual variation, ranging between 26.3% and 85.4% and 12.0% and 48.0%, respectively. Comparison of these pharmacokinetic parameters with data from previous single dose studies in the same subjects revealed a significant (p〈0.05) decrease in the clearance and an increase in the apparent bioavailability of verapamil during chronic administration, although no difference in the half-life was found. Due to the considerable variation in the oral clearance of verapamil during chronic dosing, steady-state conditions in a strict pharmacokinetic sense may never be attained, and pharmacokinetic data obtained in single dose studies will be of limited value in predicting steady-state plasma concentrations.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00546708
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  • 86
    Digitale Medien
    Digitale Medien
    Pharmacokinetic evaluation of haemoperfusion in phenobarbital poisoning (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 109-112 
    Details
    ISSN: 1432-1041
    Schlagwort(e): phenobarbital poisoning ; charcoal haemoperfusion ; distribution volume ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Charcoal haemoperfusion was performed for 5–12 h in three patients with maximal plasma phenobarbital concentrations of 600, 946 and 1044 µmol/l (138, 217 and 240 µg/ml). During haemoperfusion with constant blood flow phenobarbital elimination followed first order kinetics with half-lives of 11.1, 10.0 and 7.2 h, respectively. After termination of the haemoperfusion there was no rebound effect in plasma phenobarbital concentration and the elimination was first order with half-lives of 51, 82 and 48 h, respectively. Thus, the plasma phenobarbital half-life was reduced by 78–88% during haemoperfusion. In the same period 76–86% of the total body clearance of phenobarbital was due to the haemoperfusion column at a calculated volume of distribution of phenobarbital of 1.1–1.2 l/kg. This is clear evidence for recommending haemoperfusion in cases of serious poisoning with phenobarbital.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00546717
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  • 87
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of nadolol in healthy subjects (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 125-127 
    Details
    ISSN: 1432-1041
    Schlagwort(e): nadolol ; pharmacokinetics ; plasma levels ; urinary excretion ; bioavailability ; circadian rhythm
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 7 healthy subjects (3 males and 4 females), the kinetics of nadolol was investigated after oral doses of 60 and 120 mg. The t1/2 was 14.0±1.8 h. The peak plasma level was doubled on doubling the dose (from 69±15 to 132±27 ng/ml, respectively) and the urinary excretion (13.5%) rose similarly. The half-life of elimination was longer at night than in the day, probably because of the slower nocturnal flow of urine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00546720
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  • 88
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of furosemide in man after intravenous and oral administration. Application of moment analysis (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 197-207 
    Details
    ISSN: 1432-1041
    Schlagwort(e): furosemide ; bioavailability ; pharmacokinetics ; oral administration ; i.v. administration ; drug absorption ; moment analysis ; food effect ; dissolution effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Furosemide 40 mg was administered to 8 healthy subjects as an i.v. bolus dose, as 1 tablet in the fasting state, and as 1 tablet and a solution after food intake. The i.v. data gave a total body clearance of 162±10.8 ml/min and a renal clearance of 117±11.3 ml/min; the volume of distribution at steady state was 8.3±0.61. Oral administration gave a bioavailability of the tablet (fasting) of 51%. Food intake slightly reduced the bioavailability, but not to a significant extent. There was no significant difference in availability between the tablet and the solution. Moment analysis gave a mean residence time after the i.v. dose, MRTi.v., of 51±1.5 min. The mean absorption times (MAT) for all oral doses were significantly longer than the MRTi.v., indicating absorption rate-limited kinetics of furosemide. On average, food delayed the absorption by 60 min. The MAT for the tablet in the postprandial state was significantly longer than for the solution, indicating dissolution rate-limited absorption of the tablet.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00630286
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  • 89
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of epidural morphine in man (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 233-237 
    Details
    ISSN: 1432-1041
    Schlagwort(e): morphine ; anesthesiology ; epidural application ; pharmacokinetics ; plasma level ; CSF level
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Cerebrospinal fluid (CSF) and plasma morphine concentrations were determined in 5 patients after epidural administration of 6 mg morphine; plasma samples were collected frequently during the initial 6 h and 6–7 CSF samples were obtained from each patient over a 24 h period. Morphine was analysed using gas chromatography and electron capture detection. Individual morphine concentration-time curves were plotted for plasma and CSF and various pharmacokinetic variables were calculated. Plasma morphine concentrations after epidural injection were similar to those found after intramuscular administration; Cmax (66±8 mg/ml: mean±SEM) appeared within 12±3 min, and the terminal elimination half-life in plasma was 213±24 min. In CSF, morphine reached a peak (1575±359 ng/ml) after 135±40 min. The terminal elimination half-life for morphine in CSF was 239±10 min. The CSF bioavailability of morphine after epidural administration was calculated to be 1.9±0.5%. The study showed that epidural administration of morphine resulted in CSF concentrations many times higher than those in plasma, but still only 2% of the dose administered was available to the CSF compartment. Morphine was eliminated with similar speed from CSF and plasma.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00630291
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  • 90
    Digitale Medien
    Digitale Medien
    Pharmacokinetic and pharmacodynamic modelling with pancuronium (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 243-250 
    Details
    ISSN: 1432-1041
    Schlagwort(e): pancuronium ; neuromuscular relaxants ; simultaneous modelling ; pharmacokinetics ; pharmacodynamics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and pharmacodynamics of pancuronium were studied following intravenous infusion in eleven patients undergoing surgical anaesthesia. Measurement of the plasma concentrations (Cp) of the neuromuscular blocking agent (NMBA) and the concomitant intensities of paralysis allowed their simultaneous modelling. The pharmacokinetic parameters derived for pancuronium were in the range of previously reported values, except that the mean total systemic plasma clearance (0.79±0.28 ml·min−1·kg−1) was reduced and the mean terminal phase half-life (169 min) was longer in these patients. Plasma concentration and % paralysis data were successfully fitted to a previously proposed pharmacodynamic model. This model assumes a separate effect compartment which exchanges drug directly with the central kinetic compartment (integrated effect model). The ‘steady-state’ Cp necessary to produce 50% paralysis (ECpss(50)) was estimated to be 0.21±0.08 µg·ml−1 (mechanical response) and 0.18±0.05 µg·ml−1 (EMG response). An analysis using the Hill equation of the Cp-response relationship, during and after the constantrate infusion of pancuronium bromide, resulted in effective plasma concentrations for 50% paralysis (ECp50) of 0.35±0.06 µg·ml−1 and 0.20±0.09 µg·ml−1, respectively, for mechanical twitch response. The corresponding values for EMG response were 0.32±0.06 µg·ml−1 and 0.17±0.06 µg·ml−1. Using this latter approach, the ECp50 estimated during onset of paralysis was significantly higher than that estimated during offset of paralysis (p〈0.05); no such difference was apparent between this latter parameter and the ECpss(50) of the integrated effect model (p〉0.05). No significant differences were observed between any of the pharmacodynamic parameter estimates generated from the data obtained from the two methods of assessment of neuromuscular function (mechanical vs. EMG response) (p〉0.05).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00630293
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  • 91
    Digitale Medien
    Digitale Medien
    Effect of aluminium phosphate on the bioavailability of cimetidine and prednisolone (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 271-273 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cimetidine ; prednisolone ; aluminium phosphate ; antacids ; bioavailability ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Ten fasting subjects received 200 mg cimetidine orally either with water or 11 g aluminium phosphate mixture in a randomized, single dose, two-way cross-over study. Blood samples were taken for 12 h and urine was collected for 24 h. Cimetidine in plasma and urine was analysed by HPLC. There were no significant differences between the treatments with respect to peak plasma concentration, time to peak plasma concentration, area under the plasma concentration-time curve, and urinary excretion. In 12 healthy subjects the absorption of prednisolone was investigated when given alone and together with 11 g aluminium phosphate. Blood samples were taken over 16 h and prednisolone in plasma was analysed by HPLC. There were no significant differences in the values of area under curve (AUC), Cmax and tmax. The results indicate that aluminium phosphate does not reduce the bioavailability of cimetidine and prednisolone.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00630299
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  • 92
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of cimetidine in advanced cirrhosis (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 347-355 
    Details
    ISSN: 1432-1041
    Schlagwort(e): cimetidine ; cirrhosis ; pharmacokinetics ; bioavailability ; clearance reduction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of impaired liver function on the pharmacokinetics of cimetidine was studied in 8 patients with advanced cirrhosis given single doses of 100 mg i.v. and 400 mg p.o. on separate days. Compared to a control group of 10 healthy volunteers, the total renal and nonrenal clearance was significantly reduced in the cirrhotic patients; (total plasma clearance mean ± SD) 356±181 vs 789±262 ml/min (p〈0.01); renal clearance (Clr) 296±100 vs 588±181 ml/min (p〈0.01) and nonrenal clearance (Clnr) 97±111 vs 205±89 ml/min (p〈0.05). Compared to published results for age-matched ulcer patients, both total and nonrenal clearance were lower whereas renal clearance was within the reported normal range. A significant reduction in volume of distribution (Vdβ) was found, from 2.1±0.1 l/kg in controls to 1.0±0.4l/kg, and in the patient group there was a significant correlation between Vdβ and total plasma clearance (r=0.72, p〈0.05). Volume of distribution in steady state (Vdss) did not differ from published results in age-matched controls. No significant change in half-life was found. Bioavailability, estimated by AUC-measurement, showed considerable patient variability (21–143%), with a mean of 70±39%. This was lower than in the controls. In contrast, measurement of urinary excretion showed higher bioavailability in the patients (66±23 vs 51±8%). No correlation was found between any of the kinetic parameters and the clinical and laboratory data. It is suggested that patients with advanced cirrhosis should be closely observed when given cimetidine, and a reduction in dose should be concidered if side effects are to be avoided.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00548766
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  • 93
    Digitale Medien
    Digitale Medien
    Steady state pharmacokinetics of trimethoprim 300 mg once daily in healthy volunteers assessed by two independent methods (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 393-397 
    Details
    ISSN: 1432-1041
    Schlagwort(e): trimethoprim ; concentration ; urinary excretion ; healthy volunteers ; steady state ; pharmacokinetics ; serum creatinine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The steady state pharmacokinetics of trimethoprim was determined after 300 mg orally once daily to 6 healty volunteers for 9 days. The microbiological assay of plasma level was unreliable at trimethoprim concentrations 〉4 µg/ml, so results from an HPLC-assay are given. Steady state was present after 3 days. The plasma concentration peaked 1 to 4 h (mean 2.0 h) after the dose at a mean of 6.0 µg/ml (range 3.1–9.5 µg/ml); the minimum value was 1.5 µg/ml (range 0.6–2.9 µg/ml). The mean AUCss was 77 µg/ml · h and the mean plasma clearancess was 67 and 74 ml/min on Days 8 and 9. Renal clearance was about 60% of the plasma clearance. The average plasma half life was 10.6 h (range 8.7–15.3 h). Thus, there was considerable interindividual variation in all pharmacokinetic parameters. 72 h after the last dose trimethoprim was detectable in plasma in only 1 of the 6 subjects. The minimum urinary concentration of trimethoprim during treatment was always well above (range 22 to 220 µg/ml) the MIC values for most urinary tract pathogens. Therefore, a daily dose of 300 mg trimethoprim results in a therapeutic concentration in urine at steady state that lasts throughout the dosing interval and in most subjects probably lasts also for a further 24 h. Trimethoprim administration raised mean serum creatinine from 67 to 97 µmol/l, probably due to competitive inhibition of the tubular secretion of creatinine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00548773
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  • 94
    Digitale Medien
    Digitale Medien
    Comparison of the short-term effects of the loop diuretic piretanide and furosemide in patients with renal insufficiency (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 413-418 
    Details
    ISSN: 1432-1041
    Schlagwort(e): piretanide ; furosemide ; renal insufficiency ; loop diuretic ; natriuresis ; pharmacokinetics ; diuretic effect ; kaliuresis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The natriuretic effect of the new loop diuretic piretanide was investigated in patients with severe renal insufficiency and was compared with that of furosemide. In the first study 4 hospitalized patients (serum creatinine 407 to 1220 µmol/l) were examined after administration of piretanide (12, 24, 48 and 96 mg to two patients, and 24, 48, 96 and 192 mg to 2 other subjects, given every third day). In the second study 6 hospitalized patients (serum creatinine 194 to 698 µmol/l) were studied after receiving orally 2 different doses of piretanide and 2 different doses of furosemide orally, given every fourth day. The mean natriuretic effect of 48 mg and 96 mg piretanide was 250 and 340% of the control value for the entire group, and 311 to 480% in the subgroup of patients with serum creatinine below 530 µmol/l. For a given dose the natriuresis was inversely correlated with renal function, and at a given serum creatinine level the natriuretic response was dose-dependent. The drug had less effect on water and potassium diuresis than on natriuresis. No significant difference in natriuretic effect was found on comparison with furosemide given in the ratio furosemide: piretanide 3.33:1. The pharmacokinetic data showed a direct correlation between the dose and the mean plasma concentration and also between urinary recovery of the drug and the measured natriuretic response.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542133
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  • 95
    Digitale Medien
    Digitale Medien
    Individualizing theophylline dosage: Evaluation of a single-point maintenance dose prediction method (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 491-498 
    Details
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; computer simulation ; pharmacokinetics ; single-point dose prediction ; nomogram
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A dosage prediction method to estimate theophylline clearance and dose requirement was evaluated in 22 outpatients with partly reversible obstructive airways disease. The steady state theophylline dose required to achieve a target concentration (Css) was predicted using a single serum theophylline determination 8 h after a single oral test dose. In 17 nonsmoking patients a mean absolute deviation of 8.2% (range 0.0–21.7%) between predicted and observed Css was found, and in 5 smoking patients the mean deviation was 34.0% (range 2.2–53.8%). In 17 healthy smokers the single-point method was found to predict theophylline clearance at a sampling time of 8 h with a prediction error of 11.3 (range 0.8–25.3%) compared to the clearance determination using the area under the curve. In addition, a numerical simulation program to assess the influence of absorption, elimination and sampling time on predictive accuracy showed that the method could be successfully applied to a patient population with elimination rate constants between 0.07 1/h and 0.25 1/h, allowing a mean prediction error of 15%.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542147
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  • 96
    Digitale Medien
    Digitale Medien
    Comparison of radioreceptor assay and radioimmunoassay for atropine: Pharmacokinetic application (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 613-617 
    Details
    ISSN: 1432-1041
    Schlagwort(e): atropine ; radioreceptor assay ; radioimmunoassay ; serum levels ; pharmacokinetics ; assay comparison
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A membrane suspension prepared from rat brain was able to bind the potent muscarinic antagonist quinuclidinyl benzilate (QNB). The KD for binding was 0.48 nM and Bmax was 1.42 pmol/mg protein. Atropine competitively inhibited the binding of tritiated QNB to muscarinic receptors. This new radioreceptor assay (RRA) for atropine has been compared with a radioimmunoassay (RIA) for atropine. The RRA measures only the active component of atropine, 1-hyscyamine and in this respect it differs from the RIA. As little atropine as 1.25 ng/ml (4.33 nmol/l) in a 25 µl serum sample could be reliably assayed by the RRA. Using both assay techniques the pharmacokinetics of atropine was studied after a single 0.02 mg/kg i.v. dose given to 8 anaesthetized patients. The half-life calculated by the RRA was 3.7±2.3 h (m ± SD) and by the RIA 4.3±1.7 h. Both the volume of distribution and the total clearance were higher according to the RRA than the RIA: 3.9±1.5 vs 1.7±0.71/kg and 15.4±10.3 vs 5.9±3.6 ml/min/kg, respectively. The AUC measured by the RRA and RIA was 29.8±18.9 and 103.9±110.7 µg·h/l, respectively. The differences in the pharmacokinetics according to the 2 methods are presumably due to preferential tissue uptake of the l-form.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00543495
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  • 97
    Digitale Medien
    Digitale Medien
    Oral pharmacokinetics of omeprazole (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 641-643 
    Details
    ISSN: 1432-1041
    Schlagwort(e): omeprazole ; gastric acid secretion ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of omeprazole were studied in a group of healthy male subjects after single and repeated oral doses of 30 and 60 mg. Absorption of omeprazole from its enteric-coated formulation was unpredictable. There was a highly significant increase in the area under the plasma concentration time curve (AUC) after repeated dosing. Omeprazole increases its own relative availability following repeated dosing. This may be due to inhibition of gastric acid secretion by omeprazole which is an acid-labile compound.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00543502
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  • 98
    Digitale Medien
    Digitale Medien
    Bioavailability and pharmacokinetics of phenytoin during pregnancy (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 105-110 
    Details
    ISSN: 1432-1041
    Schlagwort(e): phenytoin ; epileptic women ; pharmacokinetics ; bioavailability ; pregnancy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration — time data were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance in nonpregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement of pregnancy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00553163
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  • 99
    Digitale Medien
    Digitale Medien
    Effect of food on pharmacokinetics of chlorambucil and its main metabolite, phenylacetic acid mustard (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 111-114 
    Details
    ISSN: 1432-1041
    Schlagwort(e): chlorambucil ; chronic lymphocytic leukaemia ; phenylacetic acid mustard ; food intake ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of food intake on the pharmacokinetics of chlorambucil (C) and its cytotoxic metabolite, phenylacetic acid mustard (PAM), has been studied in man after oral doses of chlorambucil. The administration of chlorambucil with food resulted in slower absorption than when fasting. However, the area under the plasma concentration-time curve (AUC) was unaffected. The mean ratio AUCPAM/AUCC was 2.8 (range 1.4–7.1) under fasting and 3.3 (range 1.3–7.4) under nonfasting conditions. The metabolite very probably plays an important role in the cytotoxic effects observed after administration of C, since calculations show that a major fraction of the metabolite is eliminated by alkylation reactions.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02395216
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  • 100
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of S-adenosyl-L-methionine in healthy volunteers (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 119-121 
    Details
    ISSN: 1432-1041
    Schlagwort(e): S-adenosyl-L-methionine ; pharmacokinetics ; protein binding ; dose-dependent kinetics ; healthy volunteers ; urinary excretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary S-Adenosyl-L-methionine (AdoMet) kinetics was studied in 6 male subjects given 100 and 500 mg i. v. Drug concentrations in plasma and urine were assayed using a radioenzymatic method. Pharmacokinetic parameters were estimated according to an open two-compartment model. The apparent volumes of distribution after the 100 and 500 mg doses were 407±27 and 443±36 ml/kg (mean±SEM), terminal half-lives 81±8 and 101±7 min and body clearances 3.7±0.5 and 3.1±0.2 ml/min per kg. Urinary excretion was 34±3 and 40±2% of the administered dose. The results demonstrate that drug disposition occurs more via metabolism than via renal excretion, and it is not dependent on the administered dose. Binding of AdoMet to serum proteins is negligible.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF02395218
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