Hoyo-Vadillo C, Castañeda-Hernández G, Herrera J E, Vidal-Gárate J, Salazar L A, Moreno-Ramos A, Chávez F, Tena I, Hong E
Departamento de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados del I.P.N., Mexico City, Mexico.
J Clin Pharmacol. 1989 Mar;29(3):251-6. doi: 10.1002/j.1552-4604.1989.tb03322.x.
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.
对12名墨西哥年轻健康志愿者（6名男性和6名女性）进行了口服硝苯地平的药代动力学研究，这些志愿者服用了一粒10毫克的胶囊。采用硝苯地平特异性高效液相色谱法测定血浆浓度。将实验数据进行拟合，并使用开放二室模型计算药代动力学参数。未检测到男性和女性之间有统计学上的显著差异，因此将两性视为一个单一群体。硝苯地平血浆浓度迅速上升（ka = 8.46 +/- 1.96 h-1），在0.61 +/- 0.07小时内达到最高浓度145 +/- 23 ng/ml。随后血浆浓度以分布相（α = 1.98 +/- 0.40 h-1，t1/2α = 0.46 +/- 0.06 h）和终末消除相（β = 0.17 +/- 0.03 h-1，t1/2β = 4.98 +/- 0.55 h）衰减。AUC为384 +/- 41 ng h/ml。AUC和t1/2β的值高于其他作者报道的值。AUC的差异可能归因于种族、环境因素或饮食习惯。10名受试者的血浆浓度-时间曲线中分布相清晰可辨，ka/α关系高于1.5。另外两名受试者的分布相不明显，ka/α低于1.5。结果表明，如果要将药代动力学数据用于给药方案设计，就需要对分布相进行充分表征。
