Pharmacokinetics of ozagrel and its metabolites after intravenous and oral administrations

The pharmacokinetics of ozagrel, a selective thromboxane A2 synthetase inhibitor, and its metabolites (M1 and M2) was investigated in rats. The plasma concentration-time profile of ozagrel was biexponential with a rapid terminal decay (t1/2beta, 0.173 and 0.160 h at doses of 15 and 45 mg/kg, respectively). Metabolites M1 and M2 appeared in plasma immediately after intravenous (iv) dosing of the parent drug. Similar patterns of metabolites were observed in plasma after oral dosing, although concentrations of M2 were higher than those of M1, indicating the metabolic conversion of ozagrel to M2 and M1. However, a saturable first-pass clearance was seen at a high dose (60 mg/kg) of oral ozagrel. When M2 was administered iv, M1 appeared in the circulation system at appreciable levels, providing the first evidence of metabolic conversion of M2 to M1 in the systemic circulation. Ozagrel was partly metabolized to M2 and M1 in rat intestinal mucosa, although the main metabolic site might be in the liver. The results indicate that the metabolic pathway of ozagrel in rats is the conversion of the parent drug to M2 and M1 and the conversion of M2 to M1.