Detection of drug interactions with single dose acenocoumarol: new screening method?
In this study, a design for the evaluation of drug interactions with an oral anticoagulant drug was investigated. The interaction between a single dose of acenocoumarol and cimetidine or pentobarbitone was studied. Nine healthy volunteers received three treatments: 1) 10 mg acenocoumarol in combination with cimetidine, 2) 10 mg acenocoumarol in combination with placebo, 3) 10 mg acenocoumarol after one week pretreatment with pentobarbitone. The pharmacokinetics and the pharmacodynamics of acenocoumarol were monitored for 36 h. In all subjects the plasma concentration of acenocoumarol remained consistently higher during cimetidine treatment and consistently lower after pentobarbitone pretreatment compared to placebo treatment. Cimetidine increased the anticoagulant response of acenocoumarol as measured by the Thrombotest and pentobarbitone decreased this response in all subjects. It is concluded from this study that both pharmacokinetic and pharmacodynamic drug interactions with acenocoumarol (and presumably other oral anticoagulants) can be detected after single doses, possibly obviating the use of long-term anticoagulation in healthy volunteers.
Kroon
C
C
Center for Human Drug Research, University Hospital Leiden, The Netherlands.
de Boer
A
A
Hoogkamer
J F
JF
Schoemaker
H C
HC
van der Meer
E J
EJ
Edelbroek
P M
PM
Cohen
A F
AF
D000074:Acenocoumarol / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000328:Adult; D001682:Biological Availability; D001777:Blood Coagulation / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology; D004311:Double-Blind Method; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology
D002927:Cimetidine; D010424:Pentobarbital; D000074:Acenocoumarol