title: Pharmacokinetics of losartan and its active carboxylic acid metabolite E-3174 in five ethnic populations of China.
abstract: 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 0h to the last measured point 24h [AUC((0-24))], area under the curve from 0h to infinite time [AUC((0-∞))], peak plasma concentration (C(max) ), time to reach C(max) (t(max) ), oral clearance (CL), oral volume of distribution (V(d)) and elimination half-life (t(1/2) ), were determined following a single oral dose of losartan.
  
  
  CONCLUSIONS
  The t(1/2) 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 C(max) and V(d) 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 C(max) , AUC((0-24)) , AUC((0-∞)) , CL and V(d) .
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: T
authors.initials: T
authors.lastname: Guo
authors.forename: D-Y
authors.initials: DY
authors.lastname: Xia
authors.forename: L-S
authors.initials: LS
authors.lastname: Zhao
mesh_terms: D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People / Q000208:ethnology*; D002681:China; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics*; D019808:Losartan / Q000493:pharmacokinetics*; D008297:Male; D013777:Tetrazoles / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D013777:Tetrazoles; C066026:losartan carboxylic acid; D019808:Losartan