Cimetidine-nicoumalone interaction in man: stereochemical considerations.
1. The cimetidine-nicoumalone interaction was studied in five subjects who received a single 10 mg oral dose of racemic nicoumalone alone and 3 days into an oral regimen of cimetidine of 200 mg three times daily and 400 mg at night. 2. The concentrations of R(+)- and S(-)-nicoumalone in plasma were measured using a stereospecific h.p.l.c assay; augmentation of prothrombin time was used as a measure of response. 3. Cimetidine increased the rate (but not extent) of absorption of both R(+)- and S(-)-nicoumalone, and reduced the clearance of R(+)-nicoumalone but not that of the S(-)-enantiomer. 4. Cimetidine increased the anticoagulant response produced by nicoumalone in some but not all subjects, despite a consistent effect on the pharmacokinetics of the oral anti-coagulant. 5. Cimetidine appears to produce its effect by stereoselectively inhibiting the elimination of R(+)-nicoumalone.
Gill
T S
TS
Department of Pharmacy, University of Manchester.
Hopkins
K J
KJ
Bottomley
J
J
Gupta
S K
SK
Rowland
M
M
D000074:Acenocoumarol / Q000493:pharmacokinetics / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000925:Anticoagulants; D002927:Cimetidine / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D008297:Male; D011517:Prothrombin Time; D013237:Stereoisomerism
D000925:Anticoagulants; D002927:Cimetidine; D000074:Acenocoumarol