Nifedipine: Kinetics and dynamics in healthy subjects

Kinetics and pharmacologic effects of three formulations of nifedipine were examined in six healthy young men in a crossover design. Each subject received intravenous nifedipine, 0.015 mg/kg body weight, 20 mg in a capsule, and 20 mg in a slow‐release tablet. Changes in heart rate (HR), blood pressure, heart dimensions, and plasma norepinephrine levels (PNE) were examined serially. Plasma concentrations of nifedipine (C p ) and urinary metabolite concentrations were measured by liquid chromatography. After intravenous injection the elimination t½ was 1.7 ± 0.4 hr, systemic clearance was 26.7 ± 5.4 l/hr, and volume of distribution was 0.8 ± 0.2 l/kg. After the capsule, C p rose rapidly, to a maximum concentration (C max ) of 117 ± 15 ng/ml at a maximum time (t max ) of 1.4 ± 0.5 hr. After the sustained release tablet t max was 4.2 ± 0.7 hr and C max was 26 ± 10 ng/ml. Nifedipine bioavailability was 56% ± 25% for the capsule and 52% ± 13% for the tablet, but there were large interindividual differences. Urinary excretion was 58% ± 13% 24 hr after intravenous injection, and after 32 hr was 55% ± 13% after capsules and 32% ± 8% after tablets. HR increased briefly after intravenous injection and after capsules (15 to 20 bpm), but not significantly after tablets. Diastolic blood pressure (DBP) fell briefly after capsules (8 to 10 mm Hg), but there was a sustained effect after tablets. Cardiac dimensions were unchanged. PNE levels paralleled plasma drug levels in the three experiments. There was a hyperbolic correlation between nifedipine C p and changes in DBP (r 2 = 0.86), with a minimal effective concentration of about 15 ng/ml. It is concluded that nifedipine kinetics correlate directly with the effect on blood pressure and HR. Side effects from a high C max can be avoided with the tablet. It is likely that twice‐daily dosing will induce a continued effect. Clinical Pharmacology and Therapeutics (1984) 35 , 742–749; doi: 10.1038/clpt.1984.105