Drug metabolism and disposition : the biological fate of chemicals
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Drug Metab. Dispos. · Sep 1985
Stereoselective aspects in the pharmacokinetics and pharmacodynamics of acenocoumarol and its amino and acetamido derivatives in the rat.
The stereoselectivity of the pharmacokinetics and of the pharmacodynamics of the oral anticoagulant acenocoumarol (AC) and of two of its potential metabolites, the amino (AM) and the acetamido (AA) derivatives, were investigated in the rat. The pharmacokinetics and pharmacodynamics were investigated following the acute subcutaneous (1 mg/kg) administration of the pure enantiomers. For AC and AA, the S(-)-enantiomer was preferentially eliminated, whereas for AM the R(+)-enantiomer showed the shortest half-life. ⋯ Stereoselectivity in plasma protein binding was observed, the differences, however, were small. Thus, stereoselectivity in plasma protein binding did not account for the observed differences in the pharmacokinetics. The differences in anticlotting activity between the enantiomers of AC and AM were determined mainly by their pharmacokinetics.(ABSTRACT TRUNCATED AT 250 WORDS)
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Drug Metab. Dispos. · Jul 1981
Comparative StudyQuantitative determination of the urinary excretion of ketobemidone and four of its metabolites after intravenous and oral administration in man.
The urinary excretion of ketobemidone and its metabolites has been quantified in man after intravenous and oral administration. The metabolism of ketobemidone was found to proceed via 4 metabolic pathways: N-demethylation, ring-hydroxylation, O-methylation, and conjugation. The metabolites were isolated and identified after hydrolysis of the corresponding conjugates. ⋯ Norketobemidone constituted 10-37% of the dose irrespective of route of administration. 4'-Hydroxyketobemidone amounted to 3-12% of the dose. Neither ketobemidone N-oxide nor metabolites formed after reduction of ketobemidone could be detected in the urine. Less than 2% of the dose was found in feces after iv administration.
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Drug Metab. Dispos. · Nov 1975
Change in the kinetics of sulphacetamide tissue distribution in Walker tumor-bearing rats.
The effect of Walker tumor on sulphacetamide distribution was studied in rats 21 days after tumor implantation in a hind leg. After oral administration of sulphacetamide (5 and 20 min), the concentration of the drug was found to be lower in the plasma and liver of tumor-bearing rats when compared with that of control group. However, 90 min after sulphacetamide administration, the concentration of the drug in these same tissues was found to be higher in tumor-bearing rats than in control animals. ⋯ Contrary to what was observed after oral administration, constantly higher drug concentrations were found in the plasma of tumor-bearing rats after iv injection of sulphacetamide. Furthermore, the half-life of sulphacetamide in these same animals was much higher than in control animals. It is concluded that, in Walker tumor-bearing rats, there are changes in the kinetics of sulphacetamide which are functions of the route of administration of the drug.