A population study of the pharmacokinetics of felodipine.

Abstract

1. The pharmacokinetics of felodipine was studied after continuous oral administration of 5 or 10 mg conventional tablets to a population of 140 male and female Caucasian subjects, of which 67 were hypertensive patients and 73 were healthy volunteers. In addition, 42 of these individuals received felodipine intravenously. 2. With increasing age the area under the felodipine plasma concentration vs time curve (AUC), the maximum plasma concentration (Cmax), and the terminal elimination half‐life of felodipine increased, while the plasma clearance of felodipine decreased. The bioavailability and steady state volume of distribution and the time to Cmax were not consistently influenced by age. 3. The ratio of the AUC of the primary pyridine metabolite of felodipine and that of unchanged drug decreased with increasing age. 4. Neither Cmax, AUC nor the half‐life of felodipine were related to body mass index. 5. The distribution of AUC for felodipine, as well as the ratio of the AUC of this first metabolite to that of unchanged felodipine, was unimodal. Thus, the presence of a sizable group of individuals, with a clinically significant different metabolism of 1,4‐ dihydropyridine due to genetic factors is unlikely. 6. The pharmacokinetics of felodipine did not seem to differ between hypertensive patients and healthy volunteers, when adjusted for age. Neither was there a difference between patients taking beta‐ adrenoceptor antagonists and those who did not. 7. As a group the elderly had higher total concentrations of unchanged felodipine in plasma compared with younger individuals. The variation in plasma concentrations of felodipine between individuals is, however, only partially explained by age. In clinical practice this emphasizes the need for dose titration of felodipine. 1991 The British Pharmacological Society