[Animal experiments on the pharmacokinetics of N alpha-tosyl-(3-amidinophenyl)alanine piperidide (TAPAP), a new thrombin inhibitor].

The pharmacokinetics of the synthetic thrombin inhibitor N alpha-tosyl-(3-amidinophenyl)alanine piperidide (TAPAP) was studied in rabbits using 3H-TAPAP. Concentrations in plasma, bile, urine and organs were determined by liquid scintillation counting. In plasma, moreover, the content of biologically active compound was measured by means of plasma thrombin-time determinations. After i.v. administration of doses of 1-10 mg TAPAP/kg a biphasic course of the plasma level resulted, the second phase of which has a half-time of about 5 h. This phase is considered to represent the elimination of a metabolite of TAPAP which no longer inhibits thrombin. The enteral absorption was incomplete after oral administration. Binding to plasma proteins amounted to about 50%. There was no preferential accumulation in organs or tissues. The bile contained relatively high levels of radioactivity in all routes of administration and doses studied. Elimination of TAPAP or of labelled metabolites is assumed to occur via this route.