Interruption of the enterohepatic circulation of phenprocoumon by cholestyramine.
The effect of cholestyramine (12 gm/day divided into 3 doses) on the pharmacokinetics and pharmacodynamics of a single intravenouse dose (30 mg) of phenprocoumon was studied in 6 normal subjects. Cholestyramine treatment led to an increase in the rate of elimination of phenprocoumon in all. Total clearance increased 1.5- to 2-fold. The total anticoagulant effect per dose was considerably reduced during treatment with cholestyramine. Binding studies in vitro showed that phenprocoumon is strongly bound to cholestyramine and that at a given cholestyramine concentration the percentage of phenprocoumon bound remained constant over a large concentration range of phenprocoumon. The results suggest that phenprocoumon undergoes extensive enterohepatic recycling in man which can be effectively interrupted by cholestyramine.
D015110:4-Hydroxycoumarins / Q000378:metabolism*; D000328:Adult; D002792:Cholestyramine Resin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004764:Enterohepatic Circulation / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010644:Phenprocoumon / Q000037:antagonists & inhibitors / Q000378:metabolism*
D015110:4-Hydroxycoumarins; D002792:Cholestyramine Resin; D010644:Phenprocoumon