In Vivo Pharmacokinetics of Felodipine Predicted from in Vitro Studies in Rat,Dog and Man

Abstract: The elimination of felodipine in liver microsomes from dog and man were characterized by K_m and V_max. The results were compared with previous data reported for rat. In all species studied, felodipine was primarily metabolized to its corresponding pyridine analogue. The elimination rate order was rat> dog> man. The same species difference was observed in vivo for the oral plasma clearance which was; rat 26 1/hr/kg, dog 7.5 1/hr/kg and man 4.3 1/hr/kg. The intrinsic hepatic clearance of felodipine was predicted in vitro from V_max over K_m. The in vitro values were not significantly different from those observed in vivo. Felodipine is a high-clearance drug and the in vivo extraction ratios were about the same in all species: rat 0.80, dog 0.83 and man 0.84. The extraction ratios predicted from the in vitro studies, rat 0.91, dog 0.70 and man 0.80, agreed well with those observed in vivo.