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

概要

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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 B_2 (TXB_2) , a pharmacological marker for thromboxane synthetase inhibition. Based on a quantitative relationship between the plasma ozagrel and serum TXB_2 concentrations after single oral dosage. IC_<50> and E_<max> 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 TXB_2 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 TXB_2 levels 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.
日本医療薬学会の論文
1996-02-10