Pharmacokinetics of nifedipine slow release tablet in Mexican subjects: further evidence for an oxidation polymorphism.

Nifedipine kinetics after ingestion of 20 mg slow release tablets were studied in 12 young, healthy, Mexican subjects. Plasma levels were determined by a nifedipine-specific HPLC assay. Levels rose after drug administration reaching a maximum concentration of 48.7 +/- 7.3 ng/ml in 2.1 +/- 0.7 h (mean +/- SEM). Concentrations then decayed with a terminal half-life of 16.9 +/- 3.1 hours. AUC was 526 +/- 62 ng h/ml. Five individuals were fast and seven were slow nifedipine metabolizers, according to the AUC criterion proposed by Kleinbloesem and coworkers. Individual AUC/Dose values from this and from other two studies on oral nifedipine kinetics in Mexicans were cumulated and the frequency histogram and probit analyses were performed (N = 30). A bimodal distribution was clearly observed. Fast and slow metabolizers were distinguished as those subjects with AUC/Dose values either lower or higher than 22.5 ng h/ml mg. Unlike European populations, it appears that slow metabolization is more frequent in Mexicans. Data strongly support the hypothesis of the existence of a polymorphism concerning nifedipine disposition kinetics due to genetic basis.

Pharmacokinetics of oral nifedipine: relevance of the distribution phase.

Pharmacokinetics of oral Nifedipine was studied in 12 Mexican young healthy volunteers, six men and six women, who received a 10 mg capsule. Plasma levels were determined by a nifedipine specific HPLC assay. Experimental data were fitted and pharmacokinetic parameters were calculated using an open two compartment model. No statistically significant difference was detected between men and women, thus both sexes were considered as a single population. Nifedipine plasma levels rose rapidly (ka = 8.46 +/- 1.96 h-1) reaching a maximum concentration of 145 +/- 23 ng/ml in 0.61 +/- 0.07 h. Plasma levels then decayed with a distribution phase (alpha = 1.98 +/- 0.40 h-1, t1/2 alpha = 0.46 +/- 0.06 h) and a terminal elimination phase (beta = 0.17 +/- 0.03 h-1, t1/2 beta = 4.98 +/- 0.55 h). AUC was 384 +/- 41 ng h/ml. Values of AUC and t1/2 beta were higher than those reported by other authors. Differences in the AUC could be due to ethnic origin, environmental factors or nutritional habits. Ten subjects presented plasma concentration-time curves in which the distribution phase was clearly distinguishable, having a ka/alpha relationship higher than 1.5. For the other two subjects, the distribution phase was not apparent and ka/alpha was lower than 1.5. The results show that an adequate characterization of the distribution phase is required if one pretends to use pharmacokinetic data for dosage regimen design.

[Clinical and pharmacokinetic comparison of 2 oral preparations of nifedipine: 10 mg capsules and 20 mg delayed-release tablets]. / Comparación clinica y farmacocinética de dos formulaciones orales de nifedipina: cápsula de 10 mg. y comprimido de liveración prolongada de 20 mg.

The effects and pharmacokinetic parameters of two oral formulations of nifedipine, 10 mg capsule (Adaltat) and 20 mg slow release tablet (Adalat a.p.). With the 10 mg capsule nifedipine was rapidly absorbed, reaching a maximum concentration of 120 +/- 39 ng/ml in 0.52 +/- 0.07 h, and also rapidly eliminated with an apparent halflife of 5.51 +/- 0.64 h. A fall in blood pressure and a raise in heart rate, that significantly correlated with plasma levels, were observed. 83% of the subjects reported headache, that was probably due to the sudden increase in plasma levels. With the 20 mg slow release tablet nifedipine absorption was slower, reaching a maximum concentration of 39 +/- 7 ng/ml in 1.82 +/- 0.43 h, and the apparent half-life (16.89 +/- 3.14 h) was longer than with the capsule. A fall in blood pressure was observed that significantly correlated with plasma levels; however, there was no significant correlation between these and changes in heart rate. Only 17% of the subjects reported headache. Pharmacokinetic data indicate that, in most subjects, nifedipine therapeutics plasma levels (over 15 ng/ml) can be maintained with the administration of a 20 mg slow release tablet every 12 hours. This, joined to the reduction in side effects, suggest that this formulation is the adequate alternative in chronic treatments with nifedipine, such as arterial hypertension.