Pharmacokinetics of losartan and its active carboxylic acid metabolite E-3174 in five ethnic populations of China

• Published in: Journal of clinical pharmacy and therapeutics Vol. 37; no. 2; pp. 226 - 231
• Main Authors: Yang, L., Guo, T., Xia, D.-Y., Zhao, L.-S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-04-2012; Blackwell; Hindawi Limited
• Subjects: Adult; Angiotensin II Type 1 Receptor Blockers - pharmacokinetics; Area Under Curve; Asian Continental Ancestry Group - ethnology; Biological and medical sciences; China; Chromatography, High Pressure Liquid; E-3174; ethnicity; Female; Half-Life; high-performance liquid chromatography/fluorescence; Humans; Imidazoles - pharmacokinetics; losartan; Losartan - pharmacokinetics; Male; Medical sciences; pharmacokinetics; Pharmacology. Drug treatments; Tetrazoles - pharmacokinetics; Tissue Distribution; Young Adult; Asia; China; Human; Imidazole derivatives; Tetrazole derivatives; Ethnic origin; ethnicity; high-performance liquid chromatography/fluorescence; Metabolite; Peptide hormone; HPLC chromatography; Fluorescence; Non peptide compound; Ethnic group; Octapeptide; Renin angiotensin system; E-3174; Biphenyl derivatives; Carboxylic acid; Losartan; Antihypertensive agent; Sartan derivatives; Angiotensin antagonist; Angiotensin II; Pharmacokinetics
• ISSN: 0269-4727; 1365-2710
• DOI: 10.1111/j.1365-2710.2011.01279.x

Summary
What is known and Objective:  Interethnic variability in drug pharmacokinetics is well known. Our aim was to investigate whether the pharmacokinetics of losartan and its active carboxylic acid metabolite E‐3174 vary between subjects of five Chinese ethnicities (Han, Mongolian, Korean, Hui and Uigur).
Methods:  Fifty healthy subjects (five men and five women of each ethnicity) were recruited, and each received 50‐mg dose of losartan in tablet form. Fourteen blood samples were collected for each subject over a 24‐h period after drug administration. The concentrations of losartan and its active carboxylic acid metabolite E‐3174 in plasma were determined by high‐performance liquid chromatography/fluorescence (HPLC/FLU) method, and the pharmacokinetic parameters were calculated by DAS 2.0 software and compared by SPSS 16.0 software. Pharmacokinetic parameters, including area under the curve from 0 h to the last measured point 24 h [AUC(0–24)], area under the curve from 0 h to infinite time [AUC(0–∞)], peak plasma concentration (Cmax), time to reach Cmax (tmax), oral clearance (CL), oral volume of distribution (Vd) and elimination half‐life (t1/2), were determined following a single oral dose of losartan.
Results and Discussion:  The t1/2 values of losartan and its active carboxylic acid metabolite E‐3174 showed significant differences across the five ethnicities. After normalization by weight, no ethnicity‐based difference was noted in the pharmacokinetic parameters of losartan. However, there were significant differences in Cmax and Vd of the active carboxylic acid metabolite E‐3174 for Han and Mongolian subjects, compared with the other three ethnic groups. There was a high linear correlation between weight and Cmax, AUC(0–24), AUC(0–∞), CL and Vd.
What is new and Conclusion:  Ethnicity was associated with significant differences in the single‐dose pharmacokinetics of losartan’s active carboxylic acid metabolite E‐3174 in healthy subjects of the five main ethnic groups in China.