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 (t1/2) was significantly shorter (P 0–t was lower (P 1/2, AUC0–t and AUC0–inf of E3174.
Highlights
Losartan, 2-n-butyl-4-cholo-5-hydroxymethyl-1-[(2%-(1Htetrazol-5-yl) biphenyl-4-yl)methyl] imidazole (Figure 1), an active and highly specific non-peptide angiotensin II receptor blocker, is applied for treating hypertension in clinic [1,2]
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
We aim to evaluate the bioequivalence of losartan tablets or losartan/hydrochlorothiazide tablets, compare their pharmacokinetic parameters and examine the metabolism phenotypes in healthy Chinese male volunteers
Summary
2-n-butyl-4-cholo-5-hydroxymethyl-1-[(2%-(1Htetrazol-5-yl) biphenyl-4-yl)methyl] imidazole (Figure 1), an active and highly specific non-peptide angiotensin II receptor blocker, is applied for treating hypertension in clinic [1,2]. Losartan undergoes substantial first-pass metabolism by CYP2C9, and approximately 14% of it is converted to the pharmacologically active metabolite E3174 (Figure 1). Zothiadiazines, plays a role in the renin angiotensin aldosterone (RAA) system by decreasing active sodium re-absorption and reducing peripheral vascular resistance. It is widely used in pharmaceutical formulations to make single or that combined with other antihypertensive drugs, for treating edema hypertension, diabetes insipidus, hypoparathyroidism, etc. The combination of losartan and hydrochlorothiazide is successfully used in the treatment of hypertension [8]
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