Pharmacokinetics of Hydrochlorothiazide, Losartan and E3174 after Oral Doses of Losartan and Losartan/Hydrochlorothiazide in Healthy Chinese Male Volunteers

Abstract

Aims: A simple and highly sensitive LC-MS method was used to determine the concentrations of losartan, its major active metabolite E3174 and hydrochlorothiazide in human plasma and pharmacokinetic characteristics and metabolism phenotype observation after administration of losartan tablets and losartan/hydrochlorothiazide combination tablets. Methods: An open, randomized cross-over single-dose study was designed in forty healthy male volunteers, A single-dose of 50 mg losartan tablets or 50 mg losartan/12.5 mg hydrochlorothiazide combination tablets was orally given and blood samples were collected at scheduled time. A LC-MS method was established and evaluated for determining the plasma concentrations of losartan, E3174 and hydrochlorothiazide. The pharmacokinetic parameters and characteristic of metabolism phenotypes were calculated and compared via this test. Results: The elimination rate of E3174 (t 1/2 ) was significantly shorter (P < 0.05) and the AUC 0–t was lower (P < 0.05) for administration of combination tablets. The rest of pharmacokinetic parameters of losartan and E3174 have no significant differences. Among all subjects, three phenotypes were observed: the poor, the intermediate and the extensive metabolism. Conclusion: It is indicated that the test and reference tablets were bioequivalent, and that hydrochlorothiazide could significantly alter the t 1/2 , AUC 0–t and AUC 0–inf of E3174.