Pharmacokinetic and Pharmacodynamic Modeling of a Thromboxane Synthetase Inhibitor, Ozagrel, in Human.

Abstract

Listen

Translate article

Pharmacokinetic and pharmacodynamic (PK/PD) analyses for a thromboxane synthetase inhibitor, ozagrel, were performed to predict its PK/PD profiles in human. The pharmacodynamics of ozagrel was characterized by serum levels of thromboxane B2 (TXB2), a pharmacological marker for thromboxane synthetase inhibition. Based on a quantitative relationship between the plasma ozagrel and serum TXB2 concentrations after single oral dosage, IC50 and Emax values were estimated to be 11.8 ng/ml and 94%, respectively. The pharmacokinetic parameters of ozagrel were estimated from the plasma ozagrel concentrations after intravenous (iv) bolus, iv infusion, and oral administration at various doses. An integrated, simple PK/PD model was developed to simulate the changes in serum TXB2 levels after oral administration at various doses, and the obtained simulation curves corresponded well with the observed data. In order to test the predictability of our PK/PD model, the model was then used to predict the changes in serum TXB2levels after multiple oral administration in human. The predicted curves were in good agreement with the observed date. Thus, the clinical usefulness of the PK/PD modeling was verified for ozagrel.