Pharmacokinetics of dipyridamole.

Dipyridamole, though originally introduced as a coronary vasodilator, has lately been increasingly investigated in the treatment of thromboembolic diseases because of its inhibitory influence upon blood platelet function. The compound is eliminated from the organism by hepatic biotransformation to the monoglucuronide, which almost exclusively is subjected to biliary and faecal excretion with simultaneous partial enterohepatic circulation taking place. Only minute amounts are excreted through the kidneys. In experiments on four normal human volunteers it was found that the serum concentration curve after intravenous administration of dipyridamole rather closely fits the pharmacokinetics of an open two-compartment model with first order, linear disposition kinetics and elimination taking place from the central compartment. Experiments with oral ingestion of the compound could be described by the use of a corresponding pharmacokinetic model with two consecutive first order input steps, representing the dissolution and absorption processes. The disposition rate constants (beta) were within the range of 0.0051--0.0083 min.-1 corresponding to biological half-lives of 84--145 min. The absorption rate constant was about 0.07 min.-1, and the systemic availability of an oral dose of 100 mg dipyridamole in tablets varied from 37 to 66%.