Ethnic differences in nifedipine kinetics: comparisons between Nigerians, Caucasians and South Asians.

Nifedipine was administered to 12 healthy Nigerian volunteers as a single oral dose of 20 mg capsule under fasting conditions. The pharmacokinetic results were compared with published data using the same protocol and analytical method for 27 Caucasians and 30 South Asians. The area under the plasma concentration-time curve (AUC) of nifedipine in Nigerians (808 +/- 250 ng ml-1 h) was significantly higher (P < 0.001) than that in Caucasians (323 +/- 116 ng ml-1 h) and the difference remained significant (P < 0.001) when corrected for body weight. The elimination half-life was also significantly higher (P < 0.01) in Nigerians (5.03 +/- 1.96 h) than in Caucasians (2.78 +/- 1.11 h). No significant differences were observed between Nigerians and South Asians in either AUC or half-life of nifedipine. The AUC of the nitropyridine metabolite was higher (P < 0.01) in Nigerians (220 +/- 51 ng ml-1 h) compared with that in Caucasians (154 +/- 56 ng ml-1 h) but the difference was not maintained when corrected for body weight. The AUC corrected for body weight and the elimination half-life of the metabolite were significantly higher in South Asians compared with those of Nigerians and Caucasians. The pharmacokinetics of oral nifedipine in Nigerians were similar to those in South Asians and therefore may also arise from a lower systemic clearance compared with Caucasians as has been reported previously for South Asians.

Factors affecting the absolute bioavailability of nifedipine.

1. Nifedipine was administered to eight volunteers (seven Caucasian, one East Asian of Chinese origin) as a single 10 mg capsule orally and as 2.5 mg intravenously. The pharmacokinetics were determined under fasting conditions and following 200 ml double strength grapefruit juice taken orally both 2 h before and at the time of dosing. 2. In a separate study, the pharmacokinetics of nifedipine were defined in eight South Asian volunteers (with both parents originating from the Indian subcontinent) following 10 mg nifedipine orally and 2.5 mg intravenously. 3. The administration of grapefruit juice did not alter the pharmacokinetics of intravenous nifedipine, but resulted in a significantly increased area under the plasma concentration-time curve (AUC) (191 +/- 59 c.f. 301 +/- 95 ng ml-1 h, P < 0.05) and bioavailability (0.63 +/- 0.18 c.f. 0.86 +/- 0.15, P < 0.05) following oral nifedipine. The elimination half-life was unchanged by administration of grapefruit juice and there was no evidence of decreased formation of the nitropyridine first-pass metabolite. 4. The AUC of nifedipine after intravenous administration was significantly higher in South Asian subjects than in Caucasians (146 +/- 39 c.f. 74 +/- 18 ng ml-1 h, P < 0.002). This was due to a lower systemic clearance in the South Asians which was 50% of that in the Caucasians. The half-life was markedly prolonged in South Asians (4.1 +/- 1.9 c.f. 1.7 +/- 0.5 h, P < 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)