Interruption of the enterohepatic circulation of phenprocoumon by cholestyramine

Abstract

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.

Effect of Lysine Clonixinate on the Pharmacokinetics and Anticoagulant Activity of Phenprocoumon

“…The pharmacokinetic parameters of phenprocoumon obtained in this study are similar to those which have been reported earlier following administration of single doses [5,11] and during steady-state [7]. Pharmacokinetics of phenprocoumon are characterised by low clearance (0.7−0.8 ml/min), long half-life (6−7 days) and a high degree of binding to plasma proteins (> 99 %).…”

Age-dependent differences in the anticoagulant effect of phenprocoumon in patients after heart valve surgery

“…The marked age-dependent decrease in the clearance of phenprocoumon found in this study could be caused in part by the somewhat different metabolic pattern of phenprocoumon compared to warfarin. A greater percentage of the dose of phenprocoumon is primarily glucuronidated in the liver and is subject to an enterohepatic circulation [24]. On the other hand, the kind of underlying pathology may have influenced the results.…”

Stereoselective Interaction of Phenylbutazone with [12C/13C]Warfarin Pseudoracemates in Man

“…The absorptioni of racemic warfarin was not affected even by diseases associated with severe gastrointestinal malabsorption. Cholestyramine in man interfered with the absorption of racemic warfarin causing it to appear in the stool (9), and also interfered with the absorption and subsequent hypoprothrombinemic effect of racemic phenprocoumon (10). Barbiturates did not affect the absorption of racemic warfarin, but did reduce the absorption of dicumarol (11).…”