Cheung W K, Woodward D L, Shin K, Hibberd M, Pearse S, Desjardins R E, Yacobi A, Silber B M
Medical Research Division, American Cyanamid Company, Pearl River, New York 10965.
Int J Clin Pharmacol Res. 1988;8(5):299-305.
Forty healthy male Caucasian volunteers were randomly assigned to five treatment groups to receive a placebo or a 4, 8, 12, 16 or 20 mg dose of nilvadipine. The drug was well tolerated by the subjects at all dose levels. Pharmacokinetic parameters for nilvadipine were determined using model-independent methods. There were no significant differences (p greater than 0.05) in the time to the maximum plasma concentration (Cmax) (tmax), the elimination half-life or the mean residence time among the five treatment groups. Up to doses of about 12 mg, there was a linear relationship between dose and Cmax or area under the plasma concentration-time curve (AUCO----infinity). At doses of 16 and 20 mg, the relationship between dose and Cmax or AUCO----infinity was no longer linear, suggesting that the pharmacokinetics of the drug after single oral doses greater than about 12 mg may be dose-dependent, probably due to concentration-dependent first-pass hepatic elimination of the drug.
40名健康的白人男性志愿者被随机分为五个治疗组，分别接受安慰剂或4、8、12、16或20毫克剂量的尼伐地平。在所有剂量水平下，受试者对该药物耐受性良好。使用非模型依赖方法测定尼伐地平的药代动力学参数。五个治疗组之间在达到最大血浆浓度（Cmax）的时间（tmax）、消除半衰期或平均驻留时间方面无显著差异（p大于0.05）。剂量达约12毫克时，剂量与Cmax或血浆浓度-时间曲线下面积（AUCo→∞）之间呈线性关系。在16和20毫克剂量时，剂量与Cmax或AUCo→∞之间的关系不再呈线性，这表明单次口服剂量大于约12毫克后该药物的药代动力学可能呈剂量依赖性，可能是由于药物的浓度依赖性首过肝消除。
