FELODIPINE KINETICS IN HEALTHY-MEN

Calcium antagonists are increasingly used in essential hypertension. Felodipine is a new dihydropyridine that appears to interfere wth intracellular calcium utilization. The absorption, distribution and elimination of i.v. and oral felodipine were investigated in 8 healthy men 22-31 yr old. Felodipine was given as a 2.5 mg i.v. infusion over 30 min and as a 27.5 mg oral solution. Both doses were labeled with 25 .mu.Ci 14C-felodipine. Given as an oral solution, felodipine is rapidly (mean time to peak concentration 64 min; range 30-90 min) and completely absorbed. Presystemic elimination reduced the availability to 16% (range 10%-25%). Felodipine kinetics were described by a multicompartmental model with 3 distinct phases. The t1/2 [half-life] for the initial phase was 6.4 min (range 1.7-10.4 min) and felodipine was distributed to a volume of 0.6 l/kg (range 0.4-0.9 l/kg), which approximately corresponds to the total body water. The 2nd distribution phase reached pseudoequilibrium with a t1/2 of 1.6 h (range 1.3-2.2 h). The volume of distribution at the end of this phase was 9.7 l/kg (range 6.0-18.2 l/kg). The terminal phase had t1/2 of 10.2 h (range 6.7-20.7 h). The contribution of the 3 phases to the AUC [area under the concentration] was 15%, 40% and 45% in the order of increased t1/2. Total body clearance of felodipine was 1.2 l/min (range 0.9-1.6 l/min). Within 72 h after drug dosing, 62%-81% of the felodipine doses were excreted in the urine and feces as metabolites. The rate of excretion by the kidneys had a biphasic pattern, with t1/2 values of 4 and 18 h. Approximately 10% of the doses was excreted in the feces.