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 halflife 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 the 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 3-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.
The plasma concentration versus antihypertensive effect relationship for the calcium antagonist felodipine was investigated in 67 patients with hypertension and 21 healthy subjects by use of the Emax model. No consistent effect of felodipine on blood pressure was observed in the healthy subjects. In patients with hypertension the plasma drug concentration and blood pressure versus time curves mirrored each other, indicating a close relationship between concentration and effect. The maximum effect (Emax) model fitted the diastolic blood pressure data of most patients, but the model was less often applicable in patients with low initial diastolic blood pressure levels. The average Emax values and the plasma felodipine concentration needed to obtain 50% of Emax for the patients with hypertension were 29 mm Hg and 8 nmol/L, respectively. The Emax values increased with increasing initial diastolic blood pressure levels but were similar in patients with high and low plasma felodipine concentrations. Age had negligible influence on the antihypertensive response to felodipine when compensation was made for the plasma concentrations.
1 The rate and extent of felodipine absorption from an oral solution, conventional and extended-release tablets were investigated in two groups of healthy volunteers (n = 18 + 15). 2 The antihypertensive effect of felodipine conventional tablets twice daily (n = 71) and extended-release tablets once daily (n = 76) were compared in a parallel-group study in hypertensive patients.3 As from a solution, felodipine was completely absorbed from the two solid dosage forms. The rate of absorption increased in the order extended-release tablets, conventional tablets, solution. 4 The extended-release tablet gave more sustained plasma concentrations than the conventional tablet. 5 The extended-release tablet given once daily gave similar blood pressure control to the conventional tablet given twice daily.
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