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.
Hoyo-Vadillo
C
C
Departamento de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados del I.P.N., Mexico City, Mexico.
Castañeda-Hernández
G
G
Herrera
J E
JE
Vidal-Gárate
J
J
Salazar
L A
LA
Moreno-Ramos
A
A
Chávez
F
F
Tena
I
I
Hong
E
E
D000284:Administration, Oral; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D008800:Mexico / Q000208:ethnology; D009543:Nifedipine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012737:Sex Factors
D009543:Nifedipine