Lack of effect of cimetidine on pharmacodynamics and kinetics of single oral doses of R- and S-acenocoumarol
- 1 January 1986
- journal article
- research article
- Published by Springer Nature in European Journal of Clinical Pharmacology
- Vol. 30 (5), 619-623
- https://doi.org/10.1007/bf00542424
Abstract
The kinetics and dynamics of single doses (5 mg p.o.) of the optical isomers of acenocoumarol (R-AC and S-AC) were followed in healthy subjects and the effect on them of cimetidine 800 mg/day was also investigated. The AC enantiomers differed greatly in their pharmacokinetics. The mean residence time (MRT) of R-AC was about 10 times longer than that of S-AC, 15 h vs 1.2 h. There was no difference in the volume of distribution. Depression of blood clotting activity (Thrombotest) was observed only after administration of R-AC. The inactivity of S-AC as a vitamin K antagonist must be ascribed to its short MRT. Cimetidine did not affect the acute oral kinetics of R- and S-AC, nor did it affect the anticlotting activity of R-AC. The urinary excretion pattern of the 6- and 7-hydroxylated AC metabolites was not altered during cimetidine treatment. Although the present studies showed no effect of cimetidine on the pharmacokinetics and dynamics of acenocoumarol, the findings of Serlin et al. [3] suggest that cimetidine should not be administered during acenocoumarol therapy.This publication has 20 references indexed in Scilit:
- Metabolic Fate of Phenprocoumon in HumansJournal of Pharmaceutical Sciences, 1985
- Phenylbutazone‐warfarin interaction in man: further stereochemical and metabolic considerations.British Journal of Clinical Pharmacology, 1983
- Active metabolites of acenocoumarol: do they contribute to the therapeutic effect?British Journal of Clinical Pharmacology, 1983
- Cimetidine does not increase the anticoagulant effect of phenprocoumon.British Journal of Clinical Pharmacology, 1982
- Drug Interactions with CimetidineClinical Pharmacokinetics, 1982
- Pharmacokinetics of the enantiomers of acenocoumarol in man.British Journal of Clinical Pharmacology, 1981
- CIMETIDINE: INTERACTION WITH ORAL ANTICOAGULANTS IN MANThe Lancet, 1979
- Noncompartmental Determination of the Steady‐State Volume of DistributionJournal of Pharmaceutical Sciences, 1979
- Clinical Pharmacokinetics of Oral AnticoagulantsClinical Pharmacokinetics, 1979
- Statistical moments in pharmacokineticsJournal of Pharmacokinetics and Biopharmaceutics, 1978