复方奥美沙坦酯片的人体药动学研究

Pharmacokinetics of Compound Olmesartan Medoxomil Tablets in Healthy Volunteers

关键词:  复方奥美沙坦酯片  药物动力学  高效液相色谱法  氢氯噻嗪  奥美沙坦

Key words:  compound olmesartan medoxomil tablet  pharmacokinetics  HPLC  hydrochlorothiazide  olmesartan

摘要:

目的 研究健康受试者口服复方奥美沙坦酯片的药物动力学特征。方法 30名健康受试者随机分成3组，分别空腹服用复方奥美沙坦酯片1片、2片与3片，定时取血，采用高效液相色谱法测定人血浆中氢氯噻嗪与奥美沙坦浓度并利用DAS药动学软件计算药动学参数。结果 氢氯噻嗪低中高剂量给药后的主要药动学参数分别是：t1/2为(9.68±3.37) h、(10.11±4.96) h、(11.02±4.77) h，Cmax为(69.7±19.8) μg·L-1、(158.5±62.4) μg·L-1、(209.4±85.7) μg·L-1，AUC0→τ为(737.8±110.6) μg·L-1·h、(1 397.2±252.0) μg·L-1·h、(2 200.3±517.6) μg·L-1·h；奥美沙坦低中高剂量给药后的主要药动学参数分别是：t1/2为(6.25±1.98) h、(7.99±2.43) h、(7.03±2.86) h，Cmax为(635.1±237.7) μg·L-1、(1336.8±452.0) μg·L-1、(1774.7±792.2) μg·L-1，AUC0→τ为(4438.4±1058.1) μg·L-1·h、(8239.6±1909.7) μg·L-1·h、(13150.3±3627.5) μg·L-1·h。结论 复方奥美沙坦酯片2组分在健康受试者体内为线性动力学过程。

Abstract:

OBJECTIVE The pharmacokinetics of hydrochlorothiazide and olmesartan was investigated in healthy volunteers after single administration of compound olmesartan medoxomil tablets. METHODS 30 healthy volunteers were randomly divided into 3 groups and were administered with 1, 2, 3 compound olmesartan medoxomil tablets. Venous blood was obtained timely and the concentrations of hydrochlorothiazide and olmesartan were determined by HPLC. The pharmacokinetic parameters were calculated with software DAS. RESULTS The pharmacokinetic parameters of hydrochlorothiazide of low, medium and high doses were as follows: t1/2 were (9.68±3.37)h, (10.11±4.96)h and (11.02±4.77)h, Cmax were (69.7±19.8)μg·L-1, (158.5±62.4)μg·L-1 and (209.4±85.7)μg·L-1, AUC0→τ were (737.8±110.6)μg·L-1·h, (1397.2±252.0)μg·L-1·h and (2200.3±517.6) μg·L-1·h, respectively. The pharmacokinetic parameters of olmesartan of low, medium and high doses study were as follows: t1/2 were (6.25±1.98)h, (7.99±2.43)h and (7.03±2.86)h，Cmax were (635.1±237.7)μg·L-1, (1336.8±452.0)μg·L-1 and (1774.7±792.2) μg·L-1, AUC0→τ were (4438.4±1058.1)μg·L-1·h, (8239.6±1909.7)μg·L-1·h and (13150.3±3627.5)μg·L-1·h, respectively. CONCLUSION The results suggested that the relationship of dose and AUC for compound olmesartan medoxomil tablets was linear within the dose range and there was no interaction of hydrochlorothiazide and olmesartan in healthy subjects.