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  • pharmacokinetics  (23)
  • Scanning electron microscopy  (16)
  • Springer  (39)
  • American Institute of Physics (AIP)
  • Cambridge University Press
  • 2020-2023
  • 1975-1979  (39)
  • 1935-1939
  • 1976  (39)
Collection
Keywords
Publisher
  • Springer  (39)
  • American Institute of Physics (AIP)
  • Cambridge University Press
Years
  • 2020-2023
  • 1975-1979  (39)
  • 1935-1939
Year
  • 1
    Electronic Resource
    Electronic Resource
    Comparison of the half-life of antipyrine in plasma, whole blood and saliva of man (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 327-332 
    Details
    ISSN: 1432-1041
    Keywords: Antipyrine ; pharmacokinetics ; half-life ; blood ; plasma ; saliva ; individual variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A previously described GLC method has been modified and applied to measurement of antipyrine levels in plasma, blood and saliva of man following administration of a single oral dose (10 mg/kg). The levels in blood and saliva were comparable to those in plasma at every time studied. The half life of antipyrine determined in blood, plasma or saliva in any given individual was similar. The intersubject variation in half-life was about two-fold (n=5). Antipyrine levels in saliva were not affected by the rate of saliva flow when collections were made continuously for 20 minutes. This study has demonstrated that kinetic data about antipyrine comparable to that from plasma may also be obtained from readily accessible tissue fluids, such as saliva and capillary blood.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561668
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  • 2
    Electronic Resource
    Electronic Resource
    Interindividual differences in chlorthalidone concentration in plasma and red cells of man after single and multiple doses (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 319-325 
    Details
    ISSN: 1432-1041
    Keywords: Chlorthalidone ; diuretics ; drug plasma concentration ; protein binding ; red blood-cell concentration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A gas chromatographic method has been employed to determine chlorthalidone in plasma and whole blood after therapeutic doses. Radioactively labelled chlorthalidone was used for in vitro studies of the uptake of chlorthalidone from plasma by red blood cells. Chlorthalidone was markedly concentrated in red cells and as a compartment they would account for at least 30% of total drug in the body after multiple doses. The ratio between the plasma and red cell concentration of chlorthalidone varied between individuals. After a single oral dose of 50 mg in 6 healthy volunteers chlorthalidone was eliminated with a half-life of 51 to 89 hours. The apparent volume of distribution varied between 3 and 13 1/kg and the clearance between 53 and 145 ml/min. The mean steady-state plasma concentrations during treatment with a standard dose of 50 mg daily (n=10) varied 5-fold between individuals. During the steady state approximately 50% of the daily dose was excreted unchanged in the urine during 24 hrs. The plasma levels observed in patients were higher than those predicted from the single oral dose studies in healthy volunteers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561667
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  • 3
    Electronic Resource
    Electronic Resource
    Observations on the efficacy and pharmacokinetics of sotalol after oral administration (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 367-372 
    Details
    ISSN: 1432-1041
    Keywords: Sotalol ; β-adrenoceptor blocking drugs ; exercise tachycardia ; efficacy ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of sotalol after oral administration were measured on the tachycardia induced by strenuous exercise in normal subjects. Plasma sotalol levels were also determined. The oral administration of sotalol (50, 100, 200 and 400 mg) to 6 subjects produced a progressive reduction in the tachycardia induced by severe exercise. This was similar to the effects of 25, 50, 100, 200, 400 and 800 mg given to different subjects. Each increase in sotalol dose produced a successively greater reduction in exercise tachycardia. This did not appear to be maximum even with 800 mg. Oral sotalol was rapidly absorbed and produced peak blood levels in 2 – 3 hours. The plasma levels of sotalol measured 2 hours after the oral administration of 25 to 800 mg showed never more than a six-fold variation between different subjects. The half-life of sotalol in plasma was 12.7 ± SE 1.6 hours. There was a significant correlation between the logarithm of the plasma sotalol concentration and the percentage reduction of exercise heart rate. It is concluded that the oral administration of sotalol either once or twice daily (depending on dose level) will provide satisfactory 24-hour blockade of β-adrenoceptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606550
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  • 4
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and relative bioavailability of cyclobarbital calcium in man after oral administration (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 443-450 
    Details
    ISSN: 1432-1041
    Keywords: Cyclobarbital calcium ; pharmacokinetics ; plasma concentration ; relative bioavailability ; oral administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and relative bioavailability of cyclobarbital calcium have been studied after oral administration of Phanodorm, of tablets according to the Formularium Nederlandse Apothekers (1968; FNA), and an aqueous solution. Six healthy volunteers participated in the investigation on three occasions and each received the three preparations. The dose administered was 300 mg cyclobarbital calcium. Plasma concentrations of cyclobarbital were determined at regular intervals. Absorption from the three preparations was rapid and was faster from the solution. Peak concentrations were usually attained within 1 h. The elimination of cyclobarbital could be described by a single first-order process with an average half-life of 11.6 h (range 8 – 17 h). There was little intra-subject variation of the half-life. Relative bioavailability for each volunteer was estimated by comparing the areas under the plasma concentration curves. The FNA-tablets and Phanodorm exhibited similar bioavailability, whereas the average bioavailability of the solution was 78% of that of FNA-tablets; the reason for this unexpected finding is unknown. It was concluded that cyclobarbital cannot be regarded as a uniformly suitable drug for the treatment of insomnia. The long half-life that was apparent in some of the volunteers (15 – 17 h) creates a substantial risk of residual effects on the following morning. In principle, however, the calcium salt of cyclobarbital may be used for induction of sleep, because of its rapid absorption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606563
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  • 5
    Electronic Resource
    Electronic Resource
    Clinical pharmacokinetics of sisomicin: Two-compartment model analysis of serum data after I.V. and I.M. administration (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 251-256 
    Details
    ISSN: 1432-1041
    Keywords: Sisomicin ; pharmacokinetics ; bioavailability ; two-compartment analysis ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sisomicin, a new single component aminoglycoside antibiotic related to gentamicin c1a, were determined in four healthy volunteers after intravenous and intramuscular administration of a 1 mg/kg dose. The elimination profile of this antibiotic follows two-compartment model kinetics after I.V. administration. The fast (α) and slow (β) disposition rate constants averaged 0.072 and 0.004 min−1, respectively. The volume of distribution at the steady-state averaged 0.185 liters/kg which approximately corresponds to the volume of extracellular space. The physiological availability of an intramuscular dose appeared to be complete. A method of administration adapted to the kinetic properties of the drug is proposed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558337
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  • 6
    Electronic Resource
    Electronic Resource
    Studies on hydralazine (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 311-317 
    Details
    ISSN: 1432-1041
    Keywords: Hydralazine ; instability of impaired renal function ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Following a single 50 mg dose of hydralazine (Apresoline®) in 13 patients with impaired renal function, a decrease in glomerular filtration rate (GFR) was correlated with an increase in serum half-life (T1/2) of the drug (r=−0.69; p〈0.01). The T1/2 was 15.8 h in one patient with a GFR of 16 ml·min−1, as compared to a T1/2 of 1.7–3.0 h found previously in 16 healthy volunteers. In 49 patients on long-term antihypertensive treatment with hydralazine, the ratio between the minimum steady-state drug concentration and the daily dose of hydralazine (C SS min : Dose) increased as the GFR decreased. This accumulation of the drug was particularly evident in patients with a GFR less than 30 ml·min−1 (r=−0.63; p〈0.01; n=19). As renal excretion of unchanged hydralazine is generally regarded as unimportant, the slower elimination rate in chronic renal failure was probably caused by a slower rate of metabolic conversion. It was found, however, that the renal excretion of hydralazine could easily have been underestimated, as only 12.7% of an initial hydralazine concentration of 200 ng·ml−1 in urine could be recovered after storage of the samples at room temperature for 24 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00565619
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  • 7
    Electronic Resource
    Electronic Resource
    Influence of sex on the clinical pharmacology of flutiorex, a new anorectic drug (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 325-330 
    Details
    ISSN: 1432-1041
    Keywords: Flutiorex ; pharmacokinetics ; sex ; anorectic agent ; sympathetic stimulation ; CNS stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of flutiorex, a new anorectic agent, and of a placebo on food intake and the activity of the sympathetic and central nervous systems have been compared in a double blind trial in two groups of healthy volunteers, one of five males and the other of five females. Flutiorex 20 mg orally had a significant anorectic effect both in males and females, the observed reduction in food intake being 34.0 and 27.5%, respectively. It caused α-adrenergic stimulation (blood pressure and pupil diameter) and central nervous system excitation (critical flicker frequency), both of which were more marked in males than in females. Flutiorex was better tolerated by women than by men. Measurement of the blood level of flutiorex and its de-ethylated metabolite, norflutiorex, showed that both compounds were detectable in four of the five male subjects, but in only one of the five females. Sex-linked differences in the pharmacokinetics of flutiorex may explain the greater intensity of its effects in males.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00565621
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  • 8
    Electronic Resource
    Electronic Resource
    Serum concentrations of methaqualone after repeated oral doses of a combination formulation to human subjects (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 343-347 
    Details
    ISSN: 1432-1041
    Keywords: Methaqualone ; hypnotic ; pharmacokinetics ; combination formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Concentrations of methaqualone have been measured in the serum of five male human subjects receiving five consecutive evening doses of a combination formulation containing methaqualone (250 mg), carbromal (300 mg) and benactyzine (0.33 mg) in each tablet. After administration of the first dose, mean peak serum concentrations of methaqualone (1.2 µg/ml) occurred at 3 h. After obtaining peak levels, mean concentrations of methaqualone declined rapidly during the next 6 h and there-after more slowly during the next 18 h. After administration of the last (fifth) dose, mean peak serum concentrations of methaqualone (1.9 µg/ml; 1.5 µg/ml above the predose level) occurred at 2 h. After attaining peak levels, mean concentrations of methaqualone declined rapidly during the next 6 h, and thereafter more slowly, with a half-life of approximately 10 h. Mean concentrations of methaqualone in serum samples 24 h after the second, third, fourth or fifth doses were not significantly different (0.3 µg/ml – 0.6 µg/ml) during this period of dosing. This suggests that significant accumulation of methaqualone in the serum did not occur during a period of five consecutive evening doses of the combination formulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00565624
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  • 9
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and bioavailability of indoprofen in man (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 257-262 
    Details
    ISSN: 1432-1041
    Keywords: Anti-inflammatory and analgesic drug ; indoprofen ; pharmacokinetics ; bioavailability ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a pharmacokinetic study of the new analgesic and anti-inflammatory drug indoprofen, plasma levels and urinary excretion were determined in four healthy volunteers after 100 mg and 200 mg iv, and after 100 mg (capsules) and 200 mg (tablets) oral doses. After iv administration, the mean biological half-life (t1/2 β) was about 2 h (range 1.4 to 3.2 h). The apparent volume of distribution Vdβ ranged between 11 to 17 % of body weight, indicating its limited extravascular distribution. Most of the drug was excreted in urine as glucuronide and a smaller proportion as unchanged indoprofen: the 24 h urinary excretion of these compounds accounted for 67 to 95 % of an iv dose. Peak plasma levels occurred between 30 and 120 minutes after oral administration of 100 mg as capsules or 200 mg as tablets. The mean biological half-life was about 2 h, as after iv administration. The bioavailability of oral doses was assessed using both plasma levels and urinary excretion data. The absorption of capsules and tablets was practically complete, that of the former being faster.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558338
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  • 10
    Electronic Resource
    Electronic Resource
    Effect of exchange transfusion on the elimination of digoxin in neonates (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 25-29 
    Details
    ISSN: 1432-1041
    Keywords: Digoxin ; exchange transfusion ; pharmacokinetics ; neonates ; 86Rb assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary By means of an86Rb-uptake inhibition assay, changes in the plasma concentration of digoxin and the amount of the glycoside removed during exchange transfusion have been studied in two newborns. For comparison, the exchange procedure was simulated by a computer on the basis of a two-compartment open model and available pharmacokinetic constants. A rapid decrease in plasma digoxin concentration during exchange transfusion was found when the glycoside was administered intravenously or intramuscularly within 60 min before the procedure. The amount of digoxin removed by the exchange was less than 6 per cent of the given dose. Computer simulation of the procedure also showed removal of only a minor amount of digoxin. It is concluded that the decrease in plasma concentration and the removal of only a small amount of glycoside by the exchange transfusion can be attributed mainly to extensive tissue distribution of digoxin. The results imply that replacement of digoxin after an exchange transfusion seems unnecessary.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561545
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  • 11
    Electronic Resource
    Electronic Resource
    Comparison of the pharmacokinetics of diazepam after single and subchronic doses (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 121-126 
    Details
    ISSN: 1432-1041
    Keywords: Diazepam ; pharmacokinetics ; subchronic dosage in man ; desmethyldiazepam
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In seven healthy male volunteers the effects of the pattern of dosing on the pharmacokinetics of diazepam have been studied. A cross-over design was employed that consisted of three parts: a single intravenous dose (0.1 mg/kg), and oral dosing (10 mg/day) for six days followed by an intravenous bolus (0.1 mg/kg) on the seventh day, followed by re-examination of a single intravenous dose after diazepam (D) and its major metabolite desmethyldiazepam (DD) had been completely eliminated. Plasma levels of D and DD were monitored by a specific, sensitive GLC-method. In younger patients (n=5, age 29 – 35 years) the elimination half-life, T1/2 (β), of D was 33.9±10.6 h (mean±S.D.) after the single dose. The control study gave an almost identical result (35.7±12.1). After subchronic dosage in all patients T1/2 (β) showed a modest but significant prolongation (paired t-test p〈0.01) to 52.9±17.4 h. It was caused by a significant decrease (p=0.016) in total plasma clearance ( $$\overline {\user1{Cl}} $$ ), from 26.0±10.8 ml/min to 18.2±7.0 ml/min. Older patients (age 43–60 years) showed the same phenomenon. Blood/plasma ratios remained constant indicating no change in protein binding. Biliary excretion of D was measured in five patients with a T-tube. Only negligible amounts (0.3–0.4%) of administered D were excreted within 3 days after subchronic dosage, which demonstrates a lack of enterohepatic cycling of D. After multiple administration of D, there was accumulation of DD to levels approximately five times higher than after a single dose. The possibility that the slower elimination of D after subchronic treatment might be caused by DD was also supported by experiments in dogs and rabbits. After pretreating rabbits with DD and maintaining a high DD plasma level, there was prolongation of T1/2 (β) from 2.7 h to 5.2 h, with a corresponding decrease of $$\overline {\user1{Cl}} $$ from 101.6 ml/min to 23.4 ml/min. Similar results were obtained in dogs. It is concluded that the disposition of D is altered by subchronic use and may be regulated by the plasma DD concentration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609470
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  • 12
    Electronic Resource
    Electronic Resource
    Studies on hydralazine (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 183-187 
    Details
    ISSN: 1432-1041
    Keywords: Hydralazine ; bioavailability ; pharmacogenetics ; first pass effect ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After oral administration of a single 50 mg dose of hydralazine (Apresoline®), the serum half-life (T1/2) and bioavailability (AUC0−∞) were assessed in 16 healthy volunteers. The half-life was 2.57±0.14 h (S.E.) in 10 slow acetylators of sulphadimidine, and 2.18±0.15 h in 6 fast acetylators (difference not statistically significant). AUC0−∞ was significantly higher in slow acetylators, at 1.04±0.10 µg·hour·ml−1, compared to 0.66±0.12 µg·hour·ml−1 in the fast acetylators (p〈0.025). Treatment with Apresoline® 25 mg tid produced minimum serum concentrations at steady-state of 57.3±7.3 ng·ml−1 and 33.4±4.2 ng·ml−1 in 8 slow and 5 fast acetylators, respectively (p〈0.05). The corresponding maximum concentrations were 228.8±20.3 ng·ml−1 and 147.6±15.0 ng·ml−1 in slow and fast acetylators, respectively (p〈0.025). First-pass metabolism of hydralazine could explain the difference in bioavailability of the drug between fast and slow acetylators, without any corresponding difference in the elimination rate of the drug in the post-distributive phase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558327
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  • 13
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of amitriptyline infused intravenously in man (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 337-341 
    Details
    ISSN: 1432-1041
    Keywords: Amitriptyline ; pharmacokinetics ; intravenous infusion ; two compartment model ; biological half-life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Amitriptyline was given to four male volunteers by constant rate intravenous infusion. Blood samples were collected before, during and at various times after the infusion for estimation of the serum concentrations of amitriptyline. The level of nortriptyline never reached a detectable level. A two compartment open model was shown to be applicable to the data obtained. The meaning of the parameters obtained by a non-linear, least squares curve fitting procedure is discussed and the values are compared to those recently published for nortriptyline. The calculated biological half-life of amitriptyline was about 17 hours, a figure which differs considerably from previously calculated values for volunteers, but is in accordance with some newer results from patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00565623
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  • 14
    Electronic Resource
    Electronic Resource
    Bioavailability of various preparations and doses of penicillin V (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 55-58 
    Details
    ISSN: 1432-1041
    Keywords: Penicillin V ; bioavailability ; pharmacokinetics ; dose ranging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An absorption study was performed in ten healthy volunteers to test the bioavailability of various doses of two penicillin V-K preparations: Isocillin® (Hoechst AG, Federal Republic of Germany), — tablets of 600 000 and 1.2 Mega U; V-Cillin® (Eli Lilly, USA), — tablets of 200 000, 400 000 and 800 000 U. The serum concentrations and elimination of the active substance in urine were measured for six hours after administration. Independently of the source of the preparation, a strict linear relation between the dose and the area under the serum curve (AUC), or between the dose and the urinary elimination, was demonstrated by regression analysis. The dose-dependent increase in the AUC was highly significant (p〈0.01) in the range tested, i.e. between 200 000 and 1.2 Mega U. The relative elimination of active substance in urine lay within narrow limits for all doses (35.7–41.3%). Thus, both compounds proved to have the same bioavailability.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561550
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  • 15
    Electronic Resource
    Electronic Resource
    Ampicillin: Comparison of bioavailability and pharmacokinetics after oral and intravenous administration of three brands (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 237-243 
    Details
    ISSN: 1432-1041
    Keywords: Ampicillin ; bioavailability ; pharmacokinetics ; branded products ; proprietary preparations ; capsule formulation ; tablet formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and bioavailability of three different brands of ampicillin were studied in 10 volunteers. After intravenous administration ampicillin can be described adequately by a two-compartment open pharmacokinetic model. The half-life during the α-phase was 9 min and the β-half-life was in the range 50–60 min, independent of the mode of administration. Absolute bioavailability was determined from the ratio of the areas under the serum concentration curves obtained after oral and intravenous administration of equal doses. Bioavailability was also estimated by analysis of variance. The results indicated absolute availability of the three products of 39–54%. One of the products, a capsule formulation, showed a significantly lower bioavailability than the others, which were tablet formulations.
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    URL: http://dx.doi.org/10.1007/BF00558335
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  • 16
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of butobarbital after single and multiple oral doses in man (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 263-271 
    Details
    ISSN: 1432-1041
    Keywords: Butobarbital ; pharmacokinetics ; plasma concentration ; oral administration ; accumulation ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A method is described for the assay of therapeutic levels of butobarbital (5-ethyl-5-n-butylbarbituric acid) in human plasma, which involves a single extraction step followed by gas chromatography with alkali flame ionization detection. The pharmacokinetics of butobarbital were studied in five healthy volunteers after oral administration of 200 mg. Plasma concentrations were determined at regular intervals up to 96 h and the data were fitted by non-linear, least squares regression analysis according to one-compartment kinetics. The average lag time was 0.11 h and the absorption half-life 0.21 h. The elimination half-life varied from 33.6 to 41.5 h with an average of 37.5 h. Four of the volunteers participated in a study of multiple dosing (every 24 h) during which substantial accumulation of butobarbital was observed. The elimination half-life after termination of drug administration had decreased to about 20–25% of its initial value, probably because of enzyme induction. It was concluded that butobarbital could not be regarded as a suitable drug for treatment of insomnia, since CNS depressant effects were likely to persist into the following day. Repeated administration of butobarbital should be avoided and its incidental use restricted to patients who require day-time sedation.
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    URL: http://dx.doi.org/10.1007/BF00558339
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  • 17
    Electronic Resource
    Electronic Resource
    A GLC assay for bendroflumethiazide. Preliminary data about its plasma level in man (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 293-295 
    Details
    ISSN: 1432-1041
    Keywords: Bendroflumethiazide ; diuretics ; GLC ; thiazides ; plasma level ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A GLC method for determination of bendroflumethiazide has been developed, using extractive methylation. Cyclopenthiazide was used as internal standard. The maximal plasma concentration (56–107 ng/ml) after bendroflumethiazide 10 mg given orally to four healthy volunteers was seen at 2–2.5 h. On the slope between 4 and 10 h T1/2 averaged 2.7 h.
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    URL: http://dx.doi.org/10.1007/BF00558343
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  • 18
    Electronic Resource
    Electronic Resource
    The influence of hypoglycaemic sulphonylureas on elimination and efficacy of phenprocoumon following a single oral dose in diabetic patients (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 31-36 
    Details
    ISSN: 1432-1041
    Keywords: Diabetes mellitus ; drug interaction ; phenprocoumon ; pharmacokinetics ; pharmacodynamics ; sulphonylureas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of various antidiabetic treatments on the kinetics and efficacy of a single oral dose of 12 mg phenprocoumon were studied in 71 hospitalized patients, 58 with adult-onset diabetes mellitus and 13 non-diabetic aged patients, and 13 healthy young volunteers. Treatment for one week or longer with insulin or the antidiabetic sulphonylureas tolbutamide, glibenclamide or glibornuride, altered neither the plasma level (1.29 – 1.40 µg/ml at zero time) nor the half-life of phenprocoumon (5.2 – 6.8 d) compared to treatment by diet alone. The mean half-life of phenprocoumon was significantly shorter in non-diabetic aged patients (4.2 d) than in diabetic patients of the same age (5.1 – 6.8 d), or in young healthy volunteers (5.7 d). The efficacy of a single dose of phenprocoumon (maximal reduction of Quick-values by 34 – 47% after 48 to 72 hrs) in diabetic patients treated with diet, or diet and antidiabetic drugs, was the same as in non-diabetic aged patients. In healthy young volunteers phenprocoumon was half as effective as in aged patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561546
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  • 19
    Electronic Resource
    Electronic Resource
    Postoperative disappearance of phenazone from plasma in man (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 63-68 
    Details
    ISSN: 1432-1041
    Keywords: Phenazone ; pharmacokinetics ; injuries ; surgery ; operation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The elimination rate of phenazone after a single oral dose has been studied before and after elective operations. In a group of patients with different illnesses the elimination rate was increased on the fourth to seventh days after operation but was unchanged on the second and third days. The change in elimination rate was highly significant in a standardized group of nine patients with a ligament injury in one knee studied on the fourth or fifth postoperative day. Possible reasons for the changes are discussed.
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    URL: http://dx.doi.org/10.1007/BF00561552
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    Localization of mannan at the surface of yeast protoplasts by scanning electron microscopy (1976)
    Springer
    Archives of microbiology 109 (1976), S. 9-14 
    Details
    ISSN: 1432-072X
    Keywords: Candida utilis ; Saccharomyces cerevisiae ; Colloidal gold ; Cytochemistry ; Mannan ; Plasma membranes ; Scanning electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The β(1→3)glucanase of Basidiomycete QM 806 was used to prepare Saccharomyces cerevisiae and Candida utilis protoplasts. Plasma membranes isolated from S. cerevisiae contained a small amount of mannose and traces of glucose and ribose. Randomly distributed α-mannan was detected by scanning electron microscopy at the surface of prefixed protoplasts using colloidal gold labelled with Concanavalin A as a marker. C. utilis protoplasts were also marked with anti-mannan antibodies. Again the distribution of mannan was random. This experiment indicated also that plasma membrane mannan has the same immunochemical determinants as cell wall mannan. It is hypothesized that mannan is mainly located in the outer layer of plasma membranes.
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    URL: http://dx.doi.org/10.1007/BF00425106
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    Mating in Chlamydomonas eugametos (1976)
    Springer
    Archives of microbiology 109 (1976), S. 31-35 
    Details
    ISSN: 1432-072X
    Keywords: Scanning electron microscopy ; Chlamydomonas ; Cell agglutination ; Cell fusion ; Flagella
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A technique has been developed by which mating gametes of Chlamydomonas eugametos can be studied in the Scanning Electron Microscope. A detailed description of the mating process, from the initial flagellar agglutination until the release of free vis-à-vis pairs, is presented. Flagella appear to agglutinate at random points on their surface. This is followed by a rapid increase of the contact area such that they “line-up” tip to tip. Flagella always exhibit a typical position prior to cell fusion. After cell fusion the flagella of a pair separate rapidly while the female have shortened about 33%. In a vis-à-vis pair the plasma bridge has contracted. The observations are interpreted in terms of a specific reorganization of the sexuale aggregate.
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    URL: http://dx.doi.org/10.1007/BF00425109
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    Scanning electron microscopic studies on the development of the chick retina (1976)
    Springer
    Cell & tissue research 170 (1976), S. 145-159 
    Details
    ISSN: 1432-0878
    Keywords: Neurogenesis ; Retina ; Scanning electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Fixed retinae of chick embryos and chicks of the first week after hatching were fractured and examined with the scanning electron microscope. The matrix cells of the retina proliferate up to the beginning of the second week. The migrating cells are oriented in cell cords. This columnar organization prevails up to the development of the plexiform layers formed as a consequence of the outgrowth of the dendritic and axonal cell processes. Special attention was paid to the differentiation of the ganglion, bipolar and receptor cells, and the radial fibers (Müller cells). Two main morphological patterns are significant for the organization of the retina during neurogenesis: a) the cell to cell contacts of migrating cells and b) the spatial arrangement of Müller cells which could provide guidelines for migration of neuronal elements.
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    URL: http://dx.doi.org/10.1007/BF00224296
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    A combined scanning and transmission electron microscopic study and electron probe microanalysis of human pineal acervuli (1976)
    Springer
    Cell & tissue research 174 (1976), S. 129-137 
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    ISSN: 1432-0878
    Keywords: Pineal organ, human ; Acervuli ; Scanning electron microscopy ; Transmission electron microscopy ; Electron probe microanalysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Untreated, decalcified and trypsinized acervuli from human pineal bodies were studied with the scanning and transmission electron microscope as well as by electron probe microanalysis. The mulberry-like acervuli are composed of a various number of spherical lobes (135–800 μm) between which clustered groups of globuli (4–14 urn in diameter) are observed. The acervular lobes are very probably formed by an aggregation of these globuli. Small round particles 125–500 Å in diameter are observed on the surface of the pineal concretions. These are not influenced by either decalcification or trypsin treatment. The acervular mineral corresponds morphologically to hydroxyapatite. The electron probe microanalysis reveals the existence of calcium and phosphorus as main components of the acervuli. Small quantities of magnesium and strontium were also detected.
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    URL: http://dx.doi.org/10.1007/BF00222155
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    Morphology, morphometry and electron microscopy of HeLa cells infected with bovine Mycoplasma (1976)
    Springer
    Cell & tissue research 170 (1976), S. 1-16 
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    ISSN: 1432-0878
    Keywords: Tissue culture cells ; Mycoplasma ; Light microscopy ; Transmission electron microscopy ; Scanning electron microscopy ; Morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The host-parasite relationship of HeLa M cells artificially infected with a bovine species of Mycoplasma was studied by light microscopy, transmission electron microscopy and scanning electron microscopy. The use of morphometry to quantitate some of the findings was explored. The parasites were seen in locations extracellular to the cell surface. The detection of small numbers of organisms by light microscopy was well demonstrated by use of the fluorescent antibody technique. Scanning electron microscopy proved to be an excellent method for revealing the surface details of cell-parasite morphology. Ultra-thin sections showed that the parasites are aligned mostly parallel to the plasma membrane of the host cell but separated by a gap of 10 nm. Morphometry indicated an average of 69 organisms per cell surface occupying 1.7% of the surface area. An increase of 26% in diameter of the HeLa cells, possibly as a result of infection, was observed.
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    URL: http://dx.doi.org/10.1007/BF00220107
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    A scanning electron microscope study of the development of free axonal sprouts at the cut ends of dorsal spinal nerve roots in the rat (1976)
    Springer
    Cell & tissue research 170 (1976), S. 507-513 
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    ISSN: 1432-0878
    Keywords: Axons ; Scanning electron microscopy ; Neurones, afferent ; Nerve regeneration ; Spinal nerve roots
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Rat dorsal spinal nerve roots were cut and the tip on the ganglionic side of the cut was examined by scanning electron microscopy at 0, 7, 20 and 48 h after operation. Seven hours after cutting, free axonal sprouts had started to protrude from the cut end of the nerve. After 20 h the free sprouts were more profuse than at 7 h but were smaller and had a rougher surface. At both 7 and 20 h many of the sprouts consisted of a stalk 2–7 μm in diameter with a bulbous end 5–20 μm in diameter. A few branching sprouts were seen. At 48 h the sprouts were shrunken with a deeply furrowed surface. The significance of the surface structure of the sprouts is discussed.
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    URL: http://dx.doi.org/10.1007/BF00361708
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    Effects of castration and androgen-substitution on the morphology of the epididymal epithelium of the Japanese monkey, Macacus fuscatus, as revealed by scanning electron microscopy (1976)
    Springer
    Cell & tissue research 170 (1976), S. 515-521 
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    ISSN: 1432-0878
    Keywords: Epididymal epithelium ; Castration ; Androgen-substitution ; Japanese monkey ; Scanning electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The caput epididymidis from castrated and androgen-supplemented, castrated Japanese monkeys was observed with the scanning electron microscope. The experimental findings were compared with the normal structures in control animals. The epididymal lumen of control animals was lined by a tall, pseudostratified columnar epithelium possessing long, slender stereocilia which were densely arranged in a tuft-like form. After castration, the epididymal epithelium was decreased in height to one-fifth of controls. The stereocilia were also considerably reduced in length and in number, resulting in a flattened epithelial surface with polygonal boundaries. Frequent projection of a long, single cilium from an epithelial cell into the lumen was also a prominent feature in the epididymal ducts of the castrated animals. Administration of testosterone to the castrated animals resulted in almost complete recovery of the epididymal epithelium as well as regeneration of the stereocilia which regained a tuft-like arrangement.
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    URL: http://dx.doi.org/10.1007/BF00361709
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    The aesthetes of chitons (1976)
    Springer
    Cell & tissue research 172 (1976), S. 379-388 
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    ISSN: 1432-0878
    Keywords: Chitons ; Receptors ; Shell surface ; Scanning electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The shells of the chitons Lepidochitona cinereus, Sypharochiton pelliserpentis, Amaurochiton glaucus and Onithochiton neglectus were examined by scanning electron microscopy. In all species the surface terminations of the megalaesthete and micraesthete organs could be identified lying flush with the shell surface, as well as, lenses of the shell eyes in O. neglectus. Periostracal debris and encrusting diatoms were a usual feature of the shell surfaces. The micraesthete subsidiary caps normally appear featureless, but the megalaesthete apical caps sometimes appear to be perforated. The reasons for this perforate appearance are discussed and it is concluded that it provides no evidence for the normal passage of substances out of or into the megalaesthete.
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    URL: http://dx.doi.org/10.1007/BF00399520
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    Scanning electron microscopy of bone cells in culture (1976)
    Springer
    Cell & tissue research 166 (1976), S. 65-70 
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    ISSN: 1432-0878
    Keywords: Collagen ; Bone ; Cell culture ; Scanning electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Embryonic and young rat bone cells have been grown in culture and examined in the scanning electron microscope (SEM). Compared with cells fixed in situ and taken directly from the animal, the cultured osteoblastic cells were smoother, flatter and more extensive and showed tighter intercellular contacts. Some matrix is formed in culture and undergoes at least partial mineralization as judged by the accumulation of Ca and P measured by energy dispersive x-ray analysis. Findings concerning the morphology of the collagen arrangement were indecisive. Some superficial cells, free of surrounding matrix, resembled osteocytes in normal in vivo bone. This may indicate that a proportion of the extracellular matrix produced by the cultured cells failed to polymerise into recognizable bone matrix, and that osteocytic morphology is not dependent upon the physical characteristics of the bone matrix.
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    URL: http://dx.doi.org/10.1007/BF00215125
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    Interaction of rabbit sperm and egg (1976)
    Springer
    Cell & tissue research 169 (1976), S. 277-287 
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    ISSN: 1432-0878
    Keywords: Rabbit gametes ; Cryofractography ; Scanning electron microscopy ; Transmission electron microscopy ; Zona pellucida
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Rabbit ova fertilized in vitro were prepared for scanning electron microscopy by ethanol-cryofracturing and critical-point drying methods and were also embedded and sectioned for transmission electron microscopy. Study of a region of interaction between sperm and zona pellucida with scanning electron microscopy reveals the latter to be composed of a complex network of fibers interspersed with numerous pores. Transmission electron microscopy of the same region reveals a “typical” homogeneous composition of the zona pellucida. Ultrastructural observations of thin sections passing through the region of sperm-egg interactions or through other regions of the ovum or its investments reveals very little methodological distortion of the various intracellular organelles or matrix. Application of the procedures described provides not only an elucidation of surface detail but also reveals intracellular cytoplasmic information about the same specimen during in vitro fertilization.
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    URL: http://dx.doi.org/10.1007/BF00219601
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    Experimental study of changes in osteoblastic shape induced by calcitonin and parathyroid extract in an organ culture system (1976)
    Springer
    Cell & tissue research 169 (1976), S. 449-465 
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    ISSN: 1432-0878
    Keywords: Bone ; Osteoblasts ; Cell surface ; Cell shape ; Calcitonin ; Parathyroid extract ; Scanning electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Neonate rat endocranial osteoblasts were cultured on their bone surfaces in control medium (CC) or medium to which either parathyroid extract (PTE) or calcitonin (CT) had been added for 2, 4, 8 or 24 h. Some were cultured for 24 h in CC, then for 2, 4, 8 or 24 h in either CT or PTE medium; or for 24 h in PTE, then for 2, 4, 8 or 24 h in either CC or CT; or 24 h in CT and 2, 4, 8 or 24 h in CC. The dorsal ruffling of the cells in CC was found to be suppressed by later culturing with PTE and the disoriented cells reorganized to form arrays of parallel cells. The effects of PTE were also reversed by CC or CT: the osteoblasts in the second culture (CC) lost elongation and order, and proceeded through a proliferative phase before exhibiting the ruffling form similar to a single CC 24 h culture. PTE-cultured osteoblasts showed an increase in cell overlap and contact so that a more competent barrier was formed separating the bone from the medium. In control or CT medium, however, intercellular gaps were greater than in vivo.
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    URL: http://dx.doi.org/10.1007/BF00218146
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    A critical reevaluation of the structure of the rat uriniferous tubule as revealed by scanning electron microscopy (1976)
    Springer
    Cell & tissue research 166 (1976), S. 91-100 
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    ISSN: 1432-0878
    Keywords: Kidney (rat) ; Uriniferous tubule ; Scanning electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The fine structure of luminal surface of clearly identified portions of uriniferous tubules has been studied by scanning electron microscopy to elucidate some controversies concerning the topography of certain surface formations. The results show a characteristic pattern of the luminal surface in the region of Henle's loop, which was assumed by previous authors, to belong to the collecting tubule. Furthermore it is demonstrated that no cilia are present within the terminal portion of the collecting tubules.
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    Aggregation-induced alterations in fibroblast morphology (1976)
    Springer
    Cell & tissue research 174 (1976), S. 499-518 
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    ISSN: 1432-0878
    Keywords: Fibroblast ; Human ; Transmission electron microscopy ; Scanning electron microscopy ; Aggregation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The different stages during aggregation of diploid human skin fibroblasts have been examined by transmission and scanning electron microscopy. As a result of aggregation, fibroblasts form a complex tissue configuration. Numerous intercellular junctions can be observed, while the cells remain polygonal and do not develop an organised intracellular cytoskeleton. Cell division occurs only rarely. After aggregation, signs of progressive auto-digestion develop. Adhesion to a substrate results in outgrowth of the cells and monolayer formation, even when extensive cell damage had occurred. The morphology of fibroblasts in aggregates and in the monolayers, from which they were derived, is compared and the contribution of the aggregate system to the study of fibroblast behavior is discussed.
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    URL: http://dx.doi.org/10.1007/BF00232835
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    Scanning electron microscopy of the glomerular filtration membrane in the rat kidney (1976)
    Springer
    Cell & tissue research 166 (1976), S. 299-314 
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    ISSN: 1432-0878
    Keywords: Renal glomerulus (Rat) ; Endothelial cells ; Blood capillaries ; Scanning electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The rat kidney was perfused with saline and glutaraldehyde, treated with Murakami's tannin-osmium impregnation method, ethanol-freeze cracked and dried by the critical point method. Gold-palladium evaporated specimens were observed in a field-emission scanning electron microscope. The glomerular filtration membrane, fractured in different planes was observed with the following results: 1. Adjacent pedicles originate from different podocytes. No interpedicular bridges of apparent cytoplasmic nature could be found. 2. The basement membrane, in grazing fractures shows a horizontally layered architecture. 3. The attenuated endothelial sheet (lamina fenestrata) is divided into compartments, which we suggest should be called “areolae fenestratae”, by cytoplasmic crests radiating from the nucleated portion of the endothelial cell. A crest also occurs along the cell margin, which contacts a similar crest at the margin of the adjacent cell. 4. The pores in the areolae fenestratae are variable in size (30−150 nm diameter). A knob-like projection from the apparently naked basement membrane is found in a portion of the pores. 5. Numerous microvilli may occur on the endothelium. Some of them anastomose and fuse with one another to form a net whose meshes appear identical with the endothelial pores. Domes and shelves formed of a fenestrated cytoplasmic sheet also occur above the ordinary level of the endothelial lining. A hypothesis implicating microvilli in partial renewal of the endothelial sheet is proposed. This study was assisted by Mr. K. Adachi of the SEM Laboratory at the Niigata University School of Medicine.
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    Surface morphology of lens fibers from eyes of normal and microphthalmic (Browman) rats (1976)
    Springer
    Cell & tissue research 167 (1976), S. 425-438 
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    ISSN: 1432-0878
    Keywords: Scanning electron microscopy ; Crystalline lens ; Microphthalmos
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The surface features of cortical fibers from lenses of normal adult rats and microphthalmic rats of the Browman strain have been studied by scanning electron microscopy. In the normal lenses, superficial cortical fibers follow a straight course from inner to outer pole whereas the deeper cortical fibers, while straight near the poles, pursue an undulating or zig-zag course at and near the equator. Almost all of the fibers are hexagonal in cross section and all fibers throughout their entire length are bound by interdigitating processes at each corner of the hexagon to corners of two adjacent fibers. Some fibers are also affixed by a single row of ball and socket junctions located on their broad outer and inner surfaces. Lens fibers from Browman rats display both minor and major abnormalities. These included segmentation, formation of incisures and lateral protrusions, corrugation and villous-like alteration of the broad fiber surface and development of parallel ridges on broad surfaces in a basket-weave pattern.
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    Scanning electron microscopy of photoreceptor cells in the light- and dark-adapted retina of Haplochromis burtoni (Cichlidae, Teleostei) (1976)
    Springer
    Cell & tissue research 175 (1976), S. 123-130 
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    ISSN: 1432-0878
    Keywords: Retina ; Haplochromis burtoni ; Photoreceptor cells ; Light-adaption, dark-adaption ; Scanning electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The photoreceptor layer in the retina of Haplochromis burtoni (Cichlidae, Teleostei) was studied by scanning electron microscopy. Three types of receptors were identified: rods, single-cones and double-cones. The three-dimensional arrangement of these photoreceptors is described in the light- and dark-adapted retina. The surface of the inner segment of the photoreceptor cells displays fine vertical fissures which give rise to slender processes. These so called calycal processes which are of different lengths in rods and cones, surround the beginning of the smooth-surfaced outer segment. The myoid, the contractile part of the receptor, which is located beneath the ellipsoid, was examined in the single-cones of the dark-adapted retina. It is a slender structure with surface infoldings. The myoid, studied by transmission electron microscopy, contains bundles of parallel myofilaments, which are thought to be contractile.
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    Pharmacokinetics of the antiarrhythmic disopyramide in healthy humans (1976)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 4 (1976), S. 199-230 
    Details
    ISSN: 1573-8744
    Keywords: disopyramide ; antiarrhythmic ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of the antiarrhythmic disopyramide, 4-diisopropylamino-2-phenyl-2-(2-pyridyl)butyramide phosphate, and its monodealkylated metabolite were investigated in seven volunteers after intravenous (1 and 2 mg/kg) and oral (3 and 6 mg/kg) administration. Unchanged drug (52%) and the monodealkylated metabolite (25%) were renally excreted on intravenous administration. The pharmacokinetics of disopyramide were first order and dose independent only when referenced to the drug not bound to plasma proteins since this binding was dose dependent. The apparent half-lives of the α and β phases on intravenous administration were 2 min and 4.5 hr, respectively. The apparent volumes of distribution of the central and peripheral compartments, referenced to unbound disopyramide in the plasma, were 9 and 80 liters, respectively. The half-life of absorption of oral aqueous disopyramide phosphate was 30 min with a lag time of 16 min and an apparent first-pass metabolism of 16% of the absorbed dose, consistent with the hepatic efficiency of 14%. The renal and metabolic clearances were 125 and 111 ml/min, respectively. Graphical and computer analysis of the plasma and urine data showed dose-independent first-order pharmacokinetics of plasma unbound drug in a two-compartment-body model to give two metabolites and a first-pass transformation of a fraction of the oral dose. The absorption efficiency of unchanged drug was 83%.
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    Theoretical and computational basis for drug bioavailability determinations using pharmacological data. I. General considerations and procedures (1976)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 4 (1976), S. 337-353 
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    ISSN: 1573-8744
    Keywords: bioavailability ; pharmacological data ; pharmacokinetics ; modeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The use of data deriving from monitoring the time variation of the intensity of pharmacological effect(s) following dosing can often present an advantageous alternative to the more conventional approach of using chemical or radiological assay of blood and/or urine level data for bioavailability evaluations of drug products: bioavailability studies can be performed with drugs where no assay exists. A relatively simplified discussion of the general theoretical principles on which the use of pharmacological data is based and a stepwise description of the approach for its routine application in bioavailability studies are presented. Approaches for computing rates and extents of drug bioavailability vs. time profiles on analog and digital computers are qualitatively described and quantitatively presented in a subsequent report. The concept of preabsorption (gastrointestinal bioavailability) is introduced and biophasic availability of drugs to local sites of action is discussed.
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    URL: http://dx.doi.org/10.1007/BF01063123
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    Theoretical and computational basis for drug bioavailability determinations using pharmacological data. II. Drug input ⇄ response relationships (1976)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 4 (1976), S. 355-375 
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    ISSN: 1573-8744
    Keywords: deconvolution ; bioavailability ; pharmacokinetics ; modeling ; pharmacological data
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Mathematical expressions and approaches to the computation of rates and extents of drug bioavailability for implementation on analog and digital computers are derived. The equivalency of expressions derived on the basis of assuming compartment models to an approach based on using experimentally determined weighting functions is demonstrated. The relative merits of the two techniques are discussed: their application for use with temporal pharmacological data is emphasized. The applicability of the computational techniques to determining the availability of drugs at local sites of action (biophasic availability) and to computing preabsorptive drug release into the gastrointestinal contents (gastrointestinal bioavailability) is pointed out. An approach to computationally predicting in vivo blood level or pharmacological response vs. time profiles from in vitro dissolution testing results is presented and its limitations are discussed.
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    Pharmacokinetic modeling of the dogfish shark (Squalus acanthias): Distribution and urinary and biliary excretion of phenol red and its glucuronide (1976)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 4 (1976), S. 377-388 
    Details
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; compartmental model ; phenol red ; phenol red glucuronide ; dogfish (Squalus acanthias)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A flow-limited multicompartment model simulates the distribution and disposition of phenol red in the dogfish after intravenous administration. Glucuronide conjugate, as well as parent compound, was found in urine and bile, but not in plasma, kidney, or liver tissue. An apparent 4-hr lag in phenol red appearance in the gall bladder was simulated using two stirred tanks connected in series to represent the bile ducts. The model should facilitate use of the dogfish in pharmacokinetic studies of drugs, environmental contaminants, and other xenobiotics.
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    URL: http://dx.doi.org/10.1007/BF01062827
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