Rohatagi Shashank, Lee James, Shenouda Magdy, Haworth Stephen, Bathala Mohinder Singh, Allison Mark, Rubets Igor, Heyrman Reinilde, Noveck Robert, Salazar Daniel E
Daiichi Sankyo Pharma Development, 399 Thornall Street, Edison, NJ 08837, USA.
J Clin Pharmacol. 2008 Nov;48(11):1309-22. doi: 10.1177/0091270008322176.
The pharmacokinetics of amlodipine and olmesartan in healthy volunteers after coadministration of amlodipine besylate and olmesartan medoxomil concomitantly as separate dosage forms and together in a fixed-dose combination tablet were characterized in 5 phase I, randomized, crossover studies. The mean steady-state pharmacokinetics of amlodipine and olmesartan were similar when olmesartan medoxomil 40 mg/day and amlodipine 10 mg/day were administered separately or concomitantly for 10 days. The total and maximum exposure to amlodipine and olmesartan after administration of fixed-dose combination amlodipine/olmesartan medoxomil 10 mg/40 mg was bioequivalent to amlodipine 10 mg plus olmesartan medoxomil 40 mg. The ratio of least squares mean and 90% confidence intervals for the area under the drug concentration-time curve from time zero to time t, from time zero to infinity, and the maximum observed plasma drug concentration of amlodipine and olmesartan fell within the prespecified range for bioequivalence (80.0% - 125.0%). The area under the drug concentration-time curve from time zero to time t, from time zero to infinity, and the maximum observed plasma drug concentration of both drugs also met the prespecified criterion for bioequivalence when the fixed-dose combination tablet was taken 30 minutes after a high-fat breakfast. Total exposure to amlodipine and olmesartan was dose-proportional after administration of olmesartan medoxomil 10 mg to 40 mg in the fixed-dose combination formulation with amlodipine 5 mg to 10 mg. From a pharmacokinetic perspective, the 2 drugs are well suited to coadministration in a fixed-dose combination.
在5项I期随机交叉研究中，对苯磺酸氨氯地平和奥美沙坦酯以单独剂型同时给药以及制成固定剂量复方片剂共同给药后，健康志愿者体内氨氯地平和奥美沙坦的药代动力学特征进行了研究。当奥美沙坦酯40mg/天和氨氯地平10mg/天单独给药或同时给药10天时，氨氯地平和奥美沙坦的平均稳态药代动力学相似。给予固定剂量复方制剂氨氯地平/奥美沙坦酯10mg/40mg后，氨氯地平和奥美沙坦的总暴露量和最大暴露量与氨氯地平10mg加奥美沙坦酯40mg生物等效。氨氯地平和奥美沙坦从时间零至时间t、从时间零至无穷大的血药浓度-时间曲线下面积以及最大观察到的血浆药物浓度的最小二乘均值之比和90%置信区间落在生物等效性的预定范围内（80.0% - 125.0%）。当在高脂早餐后30分钟服用固定剂量复方片剂时，两种药物从时间零至时间t、从时间零至无穷大的血药浓度-时间曲线下面积以及最大观察到的血浆药物浓度也符合生物等效性的预定标准。在固定剂量复方制剂中给予10mg至40mg奥美沙坦酯和5mg至10mg氨氯地平后，氨氯地平和奥美沙坦的总暴露量与剂量成正比。从药代动力学角度来看，这两种药物非常适合制成固定剂量复方制剂共同给药。
