PMID: 3758150Jan 1, 1986Paper

Lack of effect of cimetidine on pharmacodynamics and kinetics of single oral doses of R- and S-acenocoumarol

European Journal of Clinical Pharmacology
H H ThijssenL G Baars

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. suggest that cimetidine should not be administered during acenocoumarol therapy.

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Citations

Jan 1, 1990·Acta Pharmaceutica Nordica·G T Tucker
Oct 1, 1990·British Journal of Clinical Pharmacology·W CouetJ B Fourtillan
Dec 1, 1990·The Journal of Pharmacy and Pharmacology·L G BaarsH H Thijssen
Aug 14, 2008·Clinical Pharmacokinetics·Simone StehleUwe Fuhr
Nov 15, 1997·Scandinavian Journal of Gastroenterology·E M VreeburgG N Tytgat
Nov 1, 1988·Medical Toxicology and Adverse Drug Experience·J P AymardF Streiff
Apr 1, 1989·British Journal of Clinical Pharmacology·T S GillM Rowland
Mar 1, 1991·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·J J Hermans, H H Thijssen
Jan 27, 2004·Current Medical Research and Opinion·Gangadhar SunkaraMonica Ligueros-Saylan
Nov 1, 1988·British Journal of Pharmacology·H H ThijssenH T Vervoort-Peters
Aug 1, 1987·The Journal of Pharmacy and Pharmacology·H H Thijssen, L G Baars

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