单次及多次口服奥美沙坦酯在中国健康受试者体内药代动力学研究

目的：分析中国健康受试者单剂量或多次口服奥美沙坦酯后体内药代动力学的特征。方法单剂量实验：12名筛选合格的受试者,采用开放、随机、单剂量、三周期、3＆#215;3拉丁方设计方法将试验分为3组,每组4名,每周期分别服用相对应剂量的药物,且每周期服药前经过7 d的洗脱期。多次给药试验：12名健康受试者每天服用20 mg奥美沙坦酯,连续4 d。采集服药前0 h及服药后48 h内的血样,分析体内药物各PK参数。结果单剂量服用奥美沙坦（20、40、80 mg）后体内血浆最大浓度（Cmax）分别为（1016±349）、（1503±266）、（2516±1196） ng/ml；消除半衰期（t1/2）为（5.2±1.2）、（5.6±1.6）、（6.2±0.9）h；多次服用奥美沙坦20 mg后Cmax和t1/2分别为（894±301）ng/ml、（6.4±1.2） h,单次给药和多次给药间t1/2差异无统计学意义。单剂量试验中,当服药剂量在20∽80 mg范围,AUC0-肄、AUC0-48、Cmax等PK参数与药物剂量呈线性关系。结论奥美沙坦酯20 mg,1 d/次的给药方案在体内不会造成蓄积作用。

Pharmacokinetic study of olmesartan medoxomil in healthy Chinese sub-jects after single and multiple administrations

Objective To investigate pharmacokinetic characters of olmesartan medoxomil in healthy Chinese subjects after single and multiple administrations. Methods A single dose experiment：12 screening qualified subjects,the test wass divided into three groups by randomized-sequence,single-dose,3-treatment,3-period crossover design,each group of 4 peoples,each cycle respectively corresponding to the dose of drugs,and each cycle after 7 d washout period before taking the medicine.Multiple dosing test：12 healthy subjects were given 20 mg olmesartan medoxomil every day,contin-uous 4 d.Collected 0 h before taking the medicine and medication after blood analysis within 48 h of drugs in vivo PK parameters. Results Single dose olmesartan medoxomil （20,40,80 mg） after the maximum concentration in plasma （Cmax） were respectively （1016±349）,（1503±266）,（2516±1196） ng/ml,1/2 level elimination half-life （t1/2） for （5.2±1.2）,（5.6±1.6）, （6.2±0.9） h,after multiple dose olmesartan medoxomil,the Cmax and t1/2 was （894±301） ng/ml,（6.4±1.2） h respectively,sin-gle dose and t1/2 level differences between multiple dosing has no statistical significance.A single dose experiment,when within 20 to 80 mg dose,AUC0-∞,AUC0-48 and Cmax PK parameters with a linear relationship between dose of drug. Con-clusion Olmesartan medoxomil has no accumulation in healthy Chinese subjects after 20 mg multiple-dose.