奥美沙坦酯氨氯地平片在健康人体的药代动力学研究

目的: 建立血浆中奥美沙坦和氨氯地平浓度的LC-MS/MS测定方法,研究奥美沙坦酯氨氯地平片在健康人体的药代动力学,评价两药物的相互作用. 方法: 采用自身三交叉试验设计,24例男性健康受试者随机分成3组,分别口服奥美沙坦酯片20 mg、苯磺酸氨氯地平片6.93 mg(含氨氯地平5 mg)或奥美沙坦酯氨氯地平片(含奥美沙坦酯20 mg和氨氯地平5 mg)试验药物,给药后0~144 h间隔采集静脉血4 mL,离心分取血浆测定血药浓度,DAS 2.1.1计算药动学参数并评价是否存在药物相互作用. 结果: 单方和复方制剂中奥美沙坦主要药动学参数分别为T_max(1.80±0.70)和(2.10±0.80)h,C_max(721±225)和(637±190)ng·mL^-1,AUC_0-t(3 694±1 085)和(3 550±1 076)ng·h·mL^-1; 单方和复方制剂中氨氯地平主要药动学参数分别为T_max(5.10±2.30)和(5.60±2.20)h,C_max(2.41±0.71)和(1.99±0.56)ng·mL^-1,AUC_0-t(100±30.8)和(87.6±37.2)ng·h·mL^-1. 结论: 复方中奥美沙坦酯和苯磺酸氨氯地平在人体内无明显药物相互作用.

Objective: To establish an LC-MS/MS method for determination of olmesartan and amlodipine in plasma,and evaluate pharmacokinetics of the compound tables in healthy Chinese volunteers and discuss the drug interaction between them. Methods: In a randomized three-way crossover study,24 healthy male volunteers were divided into three groups.Volunteers in 3 groups received a single oral dose of 20 mg olmesartan medoxomil tablets,6.93 mg amlodipine besylate tablets(containing 5 mg amlodipine)or compound tablets(containing 20 mg olmesartan medoxomil and 5 mg amlodipine),respectively.Blood samples of 4 mL were obtained at different time intervals within 144 h after oral administration.The serum was separated by centrifugation for analysis.The blood concentrations of olmesartan and amlodipine were determined by LC-MS/MS,respectively.The pharmacokinetic parameters were estimated by DAS 2.1.1.The drug interaction between olmesartan and amlodipine was also discussed. Results: The main pharmacokinetic parameters of olmesartan in single and compound tablets were as follows:T_max(1.80±0.70)h and(2.10±0.80)h,C_max(721±225)ng·mL^-1and(637±190)ng·mL^-1,AUC_0-t(3 694±1 085)ng·h·mL^-1and(3 550±1 076)ng·h·mL^-1.The main pharmacokinetic parameters of amlodipine in single and compound tablets were as follows:T_max(5.10±2.30)h and(5.60±2.20)h,C_max(2.41±0.71)ng·mL^-1and(1.99±0.56)ng·mL^-1,AUC_0-t(100±30.8)ng·h·mL^-1and(87.6±37.2)ng·h·mL^-1. Conclusion: There was no significant drug interaction between olmesartan and amlodipine in healthy volunteers.