[Elimination kinetics of phenprocoumon (Marcumar) in liver cirrhosis and after premedication with phenobarbital]

Abstract

In this paper are presented the results of a study on the elimination kinetics of phenprocoumon in patients concomitantly treated with phenprocoumon and phenobarbital as well as in patients with bioptically proved hepatic cirrhosis. The pre-treatment of the patients with phenobarbital (3 X 100 mg), 4 days before phenprocoumon was started, resulted in an accelerated elimination of phenprocoumon. The biological half-life of phenprocoumon was reduced from 150 to 70 hrs when compared to normal controls, and the elimination constant was found to increase to 9,96 X 10(-3). Phenobarbital at plasma concentrations achieved by usual therapeutical dosage schedules of the drug does not interfere with the protein binding of phenprocoumon as could be shown by equilibrium dialysis. Phenobarbital, therefore, does not accelerate the elimination of phenprocoumon. The inducing effect of phenobarbital on the drug metabolizing enzyme system in the liver results in more rapid biotransformation of phenprocoumon. In patients with bioptically proved hepatic cirrhosis, the elimination kinetics did not differ from the results obtained in normal controls.