POPULATION PHARMACOKINETICS OF 2-OXO-CLOPIDOGREL IN PATIENTS WITH ACUTE CORONARY SYNDROME
The aim of the study was to develop a population pharmacokinetic (PK) model for clearance of 2-oxo-clopidogrel in patients with acute coronary syndrome (ACS). Population pharmacokinetic analysis was performed by using 72 plasma concentrations from the same number of patients (mean age of 60.82±10.76 years; total body weight (TBW) of 73.63±9.67 kg) with ACS using non-linear mixed-effect modeling (NONMEM). Validation of the final PPK model was carried out through the bootstrap analysis with 200 runs and it was used to estimate the predictive performance of the pharmacokinetic model. The typical mean value for 2-oxo-clopidogrel clearance (CL), estimated by the base model (without covariates), in our population was 39.2 l h−1.The value of aspartate transaminase and co-medication with digoxin were determinants of a derived population model. The final regression model for the clearance of 2-oxo-clopidogrel was the following: CL (lh-1) = 1.7 + 1.31*AST + 115*DIGOXIN. The derived PK model describes the clearance of 2-oxo-clopidogrel in patients with ACS, showing that the value of aspartate transaminase and co-medication with digoxin are the most important covariate. This finding will provide the basis for future PK studies.