The bioavailability and pharmacokinetics of slow release nifedipine during chronic dosing in volunteers.

Abstract

Eight healthy volunteers received slow release nifedipine 20 mg 12 hourly, for six doses. A nifedipine pharmacokinetic profile was performed after the fifth dosing interval using 12 sampling times over 12 h. A specific high pressure liquid chromatography (h.p.l.c.) nifedipine assay was used. Six of the volunteers subsequently received an i.v. infusion of 3.5 mg of nifedipine after an identical period (five dosing intervals) of chronic oral dosing with slow release nifedipine 20 mg 12 hourly. An identical pharmacokinetic profile was performed after the infusion. Bioavailability, clearance (CL), apparent volume of distribution (V), apparent half life (t1/2) and area under the curve (AUC) were calculated. The geometric mean apparent t1/2 for the slow release preparation was 6.3 +/‐ 2.0 h. In the six volunteers, the mean bioavailability was 46% (range 29‐86%), the mean CL was 588.0 +/‐ 67.1 ml min‐1, the mean apparent V was 160.1 +/‐ 61.7 l. The pharmacokinetics of slow release nifedipine during chronic dosing appear similar to those derived from single dose studies.

Single Dose and Steady-State Pharmacokinetic Profiles of Nifedipine GITS Tablets in Healthy Elderly and Young Volunteers

“…Although several pharmacokinetic studies on nifedipine retarded-release formulations have concentrated on young, healthy subjects (A vgerinos & Gorrod 1990;Debbas et al 1986;Kohri et al 1987;Leucuta 1988;Ohnishi et al 1987;Saano et al 1989) or hypertensive patients (Murdoch & Brogden 1991), the possibility of age-related changes in nifedipine pharmacokinetics have only recently been investigated (Robertson et al 1988;Scott et al 1988). The present study was carried out to compare the acute and steady-state pharmacokinetics of the nifedipine GITS tablet formulation in healthy elderly and young volunteers, and to evaluate the safety of nifedipine GITS in these populations.…”

Mechanistic Framework to Predict Maternal‐Placental‐Fetal Pharmacokinetics of Nifedipine Employing Physiologically Based Pharmacokinetic Modeling Approach

“…7,10 Different physiological changes take place during pregnancy, which can alter drug exposure. 11 Following multiple administrations of 20-mg nifedipine slow-release tablets every 12 hours, the area under the plasma concentration-time curve from time 0 to 12 hours in women at labor (120 ng•h/mL) 12 was found to be approximately 60% lower than in the nonpregnant population (300 ng•h/mL) 13 under the same dosing regimen. This decreased nifedipine exposure during pregnancy was largely attributed to the cytochrome P450 (CYP) 3A4 metabolism 14 that is induced during pregnancy reaching about 2.3-fold.…”