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  • Articles  (164)
  • pharmacokinetics  (164)
  • 1980-1984  (164)
  • Medicine  (164)
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  • Articles  (164)
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  • 1
    Electronic Resource
    Electronic Resource
    Distribution of oral ketoconazole to vaginal tissue (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 331-333 
    Details
    ISSN: 1432-1041
    Keywords: ketoconazole ; vaginal candidosis ; oral antimycotic ; distribution ; pharmacokinetics ; vaginal tissue concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma samples and biopsies of vaginal tissue were obtained from 23 healthy women undergoing operative sterilization, 1 to 6 h after a single oral dose of ketoconazole 200 mg. Drug concentrations in plasma and tissue, were measured by a specific gas chromatographic method. The vaginal tissue concentration averaged 2.4 times less than the corresponding plasma levels. Equilibrium between tissue, and plasma was established within 1 h after dosing, when vaginal tissue levels exceeded 1 µg/g. Ketoconazole concentrations decayed monoexponentially over the time interval studied (1–6 h), with the similar half-lives of 1.2 and 1.4 h in plasma and tissue, respectively. Following an oral 200 mg dose, a tissue concentration not less than 0.01 µg/ml was maintained over a 12 h period. This concentration has been shown to prevent outgrowth of the invasive (pseudo) mycelial form ofCandida albicans. Hence, a b.i.d. or t.i.d. dosage schedule of ketoconazole in vaginal candidosis would give continuously effective levels at the site of infection. Ketoconazole concentrations in vaginal fluid are thought to be much higher than in the tissue because of ion-trapping. The present data may explain the efficacy of oral ketoconazole in the treatment of vaginal candidosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613615
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  • 2
    Electronic Resource
    Electronic Resource
    Plasma and salivary pharmacokinetics of caffeine in man (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 45-52 
    Details
    ISSN: 1432-1041
    Keywords: caffeine ; pharmacokinetics ; plasma ; saliva ; urinary elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609587
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  • 3
    Electronic Resource
    Electronic Resource
    Elimination of cefroxadine (CGP-9000) from patients undergoing dialysis (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 109-112 
    Details
    ISSN: 1432-1041
    Keywords: cefroxadine ; haemodialysis ; pharmacokinetics ; terminal renal impairment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cefroxadine was studied in 17 patients with terminal renal impairment, 10 of whom were undergoing 5 h dialysis sessions. The antibiotic was administered as a single oral dose of 500 mg. Cefroxadine followed a single compartment open kinetic model. During the interdialysis period in patients with terminal renal impairment, an average Cmax of 26.59 µg/ml and a tmax of 3.65 h were reached, which are greater than in patients with normal renal function. The serum half-life was reduced from 23.55 h in the interdialysis periods to 3.40 h during the dialysis sessions. The average extraction coefficient was 0.249. It is recommended that a 500 mg dose cefroxadine should be administered at the end of each dialysis session if the interdialysis period is 48 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613936
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  • 4
    Electronic Resource
    Electronic Resource
    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
    Keywords: sodium valproate ; epileptic patients ; pharmacokinetics ; plasma concentration ; prediction ; maintenance dosage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561679
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  • 5
    Electronic Resource
    Electronic Resource
    Paracetamol pharmacokinetics in thyroid disease (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 269-273 
    Details
    ISSN: 1432-1041
    Keywords: paracetamol ; thyrotoxicosis ; hypothyroidism ; drug disposition ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption, distribution and elimination of oral paracetamol have been studied in patients before and after treatment of thyrotoxicosis (n=7) and hypothyroidism (n=4). Absorption was faster in patients with untreated thyrotoxicosis than when subsequently euthyroid. The peak paracetamol concentration, however, was lower in thyrotoxic patients due to an apparent increase in the total body clearance and a shorter plasma half-life. Both absorption and elimination rates were reduced in hypothyroid patients, but were not significantly different from the euthyroid results. When estimated using a two compartment model the total volume of distribution and the hybrid distribution rate constants were unrelated to thyroid status, but the apparent volume of the central compartment was significantly greater in the thyrotoxic group. These changes in drug disposition may contribute to differences in drug response seen in thyroid disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563010
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  • 6
    Electronic Resource
    Electronic Resource
    Difference between single and multiple dose pharmacokinetics of orphenadrine hydrochloride in man (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 343-350 
    Details
    ISSN: 1432-1041
    Keywords: orphenadrine ; single dose ; multiple doses ; bioavailability ; pharmacokinetics ; N-demethylorphenadrine ; metabolism ; dog ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of orphenadrine were measured by a specific gaschromatographic method in 5 healthy male volunteers after a single oral dose of orphenadrine hydrochloride 100mg. The single dose pharmacokinetic profile of orphenadrine was evaluated from these data. The elimination half-life ranged from 13.2–20.1 h after the commercial tablet formulation. Plasma concentrations, determined in volunteers and patients under different conditions of repeated oral administration of the same formulation of orphenadrine hydrochloride exceeded the theoretical values, predicted from the single dose pharmacokinetics, by a factor 2 to 3. The elimination half-lives after discontinuation of treatment showed a 2 to 3-fold increase over the single dose values. This demonstrates a clear discrepancy between the multiple and single dose pharmacokinetics of orphenadrine. Experiments in dogs suggested competition for biotransformation between orphenadrine and its metabolite N-demethylorphenadrine. Product inhibition of this type could explain the observed discrepancy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637624
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  • 7
    Electronic Resource
    Electronic Resource
    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
    Keywords: cefoxitin ; beta-lactam antibiotics ; pharmacokinetics ; serum concentration ; pleural fluid concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548772
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  • 8
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of intravenous and oral tolmesoxide (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 119-125 
    Details
    ISSN: 1432-1041
    Keywords: tolmesoxide ; metabolite ; volunteers ; pharmacokinetics ; intravenous ; oral ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A high pressure liquid chromatographic assay was developed for simultaneous measurement of the plasma levels of tolmesoxide and its principal metabolite, RX71112. The assay was used to study the disposition of intravenous and oral tolmesoxide in ten normotensive subjects. Two exponential terms were required to describe the disposition of the drug following intravenous administration, whilst a single exponential term sufficied to account for the decay in the plasma concentration after oral administration. The bioavailability of oral tolmesoxide from capsules averaged 84.5% and was independent of dose. The mean half-life after i. v. dosing was 2.6 h (±0.3 SEM) compared to values of 1.9 h (±0.1 SEM) and 2.7 h (±0.5 SEM) following 200 and 400 mg oral doses respectively. In all subjects RX71112 appeared in plasma shortly after tolmesoxide following both routes of administration. The terminal half-life of the metabolite was significantly longer than tolmesoxide with a mean value of 4.9 h (±0.9 SEM) following the 200 mg oral dose of tolmesoxide. The binding of tolmesoxide and RX71112 at therapeutic plasma concentration was 36.8% (±0.5 SEM) and 58.5% (±0.3 SEM) and this remained unchanged at higher concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00568398
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  • 9
    Electronic Resource
    Electronic Resource
    Clinical pharmacokinetics and pharmacodynamics of fazadinium in renal failure (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 293-298 
    Details
    ISSN: 1432-1041
    Keywords: neuromuscular relaxants ; fazadinium ; pharmacokinetics ; renal failure ; neuromuscular transmission
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic behaviour and neuromuscular blockade produced by the administration of fazadinium bromide at a dose of 1 mg/kg have been studied in seven patients with end-stage renal failure. No significant differences were found in the pharmacokinetic or pharmacodynamic properties when compared with patients with normal renal function. It is suggested that fazadinium may be superior to either d-tubocurarine or pancuronium in providing muscle relaxation for patients with renal failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00618780
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  • 10
    Electronic Resource
    Electronic Resource
    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
    Keywords: dexamethasone ; bioavailability ; pharmacokinetics ; ‘first-pass’ effect ; pre-systemic elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613935
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