Population pharmacokinetics of atorvastatin, simvastatin and pravastatin after oral administration in humans

ABSTRACT

The purpose of this study is to determine the population pharmacokinetics of 3 statins after oral dosing. This was achieved by simultaneous data fitting of 101 different individuals from three studies 25 subjects for pravastatin, 40 subjects for simvastatin and 36 subjects for atorvastatin. Each study was fitted separately. Plasma profiles were best characterized by 1 -compartment model for pravastatin, 2-compartment model for simvastatin, and 3 -compartment model for atorvastatin. The criteria used for model building involved the examination of the fitted cuves, the improvement in objective function and statistical tests Akaike test, Schwarz test and log likelihood test; and examining the improvement in residual plots. The elimination rate constant and clearance values for pravastatin is higher than simvastatin and higher than atorvastatin which is in agreement with models used. The variability, as indicated by population coefficient of variation, is generally higher than 30% rendering them highly variable drugs