Tateishi T, Okumura K, Orii Y, Tanaka T
Department of Clinical Pharmacology, Hirosaki University School of Medicine, Hirosaki, Aomori, Japan.
Int J Clin Pharmacol Ther. 2004 Jan;42(1):58-62. doi: 10.5414/cpp42058.
To examine the reproducibility of nifedipine absorption from gastrointestinal therapeutic system (GITS) tablets by comparing the single-dose pharmacokinetic profiles of 4 different dosages administered orally.
Twelve healthy male volunteers, aged between 22 and 29 years were enrolled in the open, 4-way, dose escalation study with single oral doses of 10, 20, 40 and 60 mg (two 30 mg) nifedipine GITS tablets. Each administration was separated by a 1-week washout period. Coefficients of variation (CV) of dose-corrected area under the concentration-time curve (AUC) and peak plasma drug concentrations (Cmax) were calculated from the pharmacokinetic profiles.
Mean AUC and mean Cmax were dose-proportional from 10 to 60 mg. Although the CV of 4 mean dose-corrected AUC and Cmax were 5.5% and 17.5%, respectively, CV of dose-corrected AUC and Cmax in each subject varied from 5.1 to 37.4% (mean 11.0%) and from 14.1% to 46.4% (mean 25.8%), respectively.
Whereas mean plasma nifedipine concentration remained markedly stable over a 16- to 24-hour interval and mean dose-corrected AUC showed good reproducibility with nifedipine GITS, the CV of dose-corrected AUC of the nifedipine GITS tablets in each subject showed large variability.
通过比较口服4种不同剂量硝苯地平胃肠道治疗系统（GITS）片的单剂量药代动力学曲线，考察其吸收的重现性。
12名年龄在22至29岁之间的健康男性志愿者参与了这项开放、4种剂量递增的研究，单次口服10、20、40和60毫克（两片30毫克）硝苯地平GITS片。每次给药间隔1周的洗脱期。根据药代动力学曲线计算剂量校正浓度-时间曲线下面积（AUC）和血浆药物峰浓度（Cmax）的变异系数（CV）。
10至60毫克时，平均AUC和平均Cmax与剂量成正比。虽然4个平均剂量校正AUC和Cmax的CV分别为5.5%和17.5%，但每个受试者的剂量校正AUC和Cmax的CV分别在5.1%至37.4%（平均11.0%）和14.1%至46.4%（平均25.8%）之间变化。
虽然硝苯地平平均血浆浓度在16至24小时间隔内保持明显稳定，且硝苯地平GITS的平均剂量校正AUC显示出良好的重现性，但每个受试者硝苯地平GITS片的剂量校正AUC的CV显示出较大的变异性。
