PHARMACOKINETICS OF OZAGREL AND ITS METABOLITES AFTER INTRAVENOUS ANDORAL ADMINISTRATIONS

The pharmacokinetics of ozagrel, a selective thromboxane A(2) syntheta se inhibitor, and its metabolites (Mi and M2) was investigated in rats . The plasma concentration-time profile of ozagrel was biexponential w ith a rapid terminal decay (t(1/2 beta), 0.173 and 0.160 h at doses of 15 and 45 mg/kg, respectively). Metabolites M1 and M2 appeared in pla sma immediately after intravenous (iv) dosing of the parent drug. Simi lar patterns of metabolites were observed in plasma after oral dosing, although concentrations of M2 were higher than those of M1, indicatin g the metabolic conversion of ozagrel to M2 and M1. However, a saturab le first-pass clearance was seen at a high dose (60 mg/kg) of oral oza grel. When M2 was administered iv, M1 appeared in the circulation syst em at appreciable levels, providing the first evidence of metabolic co nversion of M2 to M1 in the systemic circulation. Ozagrel was partly m etabolized to M2 and M1 in rat intestinal mucosa, although the main me tabolic site might be in the liver. The results indicate that the meta bolic pathway of ozagrel in rats is the conversion of the parent drug to M2 and M1 and the conversion of M2 to M1.