Pharmacokinetics of Dipyridamole

Abstract

Dipyridamole, though originally introduced as a coronary vasodilator, has lately been increasingly investigated in the treatment of thromboembolic diseases because of its inhibitory influence on blood platelet function. The compound is eliminated from the organism by hepatic biotransformation to the monoglucuronide, which almost exclusively is subjected to biliary and fecal excretion with simultaneous partial enterohepatic circulation taking place. Only minute amounts are excreted through the kidneys. In experiments on 4 normal human volunteers the serum concentration curve after i.v. administration of dipyridamole rather closely fits the pharmacokinetics of an open 2-compartment model with 1st order, linear deposition 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 2 consecutive 1st 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%.