FACTORS AFFECTING THE ABSOLUTE BIOAVAILABILITY OF NIFEDIPINE

1 Nifedipine was administered to eight volunteers (seven Caucasian, on e East Asian of Chinese origin) as a single 10 mg capsule orally and a s 2.5 mg intravenously. The pharmacokinetics were determined under fas ting conditions and following 200 mi double strength grapefruit juice taken orally both 2 h before and at the time of dosing. 2 In a separat e study, the pharmacokinetics of nifedipine were defined in eight Sout h Asian volunteers (with both parents originating from the Indian subc ontinent) following 10 mg nifedipine orally and 2.5 mg intravenously. 3 The administration of grapefruit juice did not alter the pharmacokin etics of intravenous nifedipine, but resulted in a significantly incre ased area under the plasma concentration-time curve (AUG) (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 elimi nation half-life was unchanged by administration of grapefruit juice a nd there was no evidence of decreased formation of the nitropyridine f irst-pass metabolite. 4 The AUC of nifedipine after intravenous admini stration was significantly higher in South Asian subjects than in Cauc asians (146 +/- 39 c.f. 74 +/- 18 ng ml(-1) h, P < 0.002). This was du e to a lower systemic clearance in the South Asians which was 50% of t hat in the Caucasians. The half-life was markedly prolonged in South A sians (4.1 +/- 1.9 c.f: 1.7 +/- 0.5 h, P < 0.002). 5 The oral administ ration of nifedipine resulted in a significantly higher AUC of nifedip ine in the South Asian compared with the Caucasian volunteers (402 +/- 198 c.f: 187 +/- 62 ng ml(-1) h, P < 0.05). However, the bioavailabil ity was similar at 0.64, suggesting that reduced systemic clearance is the cause of the differences in AUCs observed with both routes of adm inistration. Consistent with this, the elimination half-life was prolo nged in the Asians (5.3 +/- 1.5 c.f: 2.6 +/- 1.1 h, P < 0.01). The AUC of the nitropyridine first-pass metabolite was similar in the two gro ups. 6 These data on the bioavailability and systemic clearance of nif edipine indicate that intestinal and hepatic CYP3A activities may be i nfluenced independently by environmental and/or genetic factors.