title: Pharmacokinetic properties and bioequivalence of two irbesartan/ hydrochlorothiazide fixed-dose combination tablets in healthy male Chinese volunteers.
abstract: OBJECTIVE
  The aim of the present study was to compare the pharmacokinetic profiles between a new generic and a branded reference formulation of irbesartan/ hydrochlorothiazide FDC tablets, and to assess the bioequivalence of the two products in healthy Chinese male volunteers.
  
  
  METHODS
  24 male healthy volunteers participated in the open-label, single-dose, randomized-sequence, 2-way crossover study. Eligible subjects were randomly assigned (1:1) to receive a single 300/12.5-mg dose of either the test or reference formulation followed by a 1-week washout. Blood samples were obtained before (0 hours) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48, and 72 hours after dosing. Plasma concentrations of irbesartan and hydrochlorothiazide were analyzed by two separate validated liquid chromatography/tandem mass spectrometric (LC-MS/MS) methods.
  
  
  RESULTS
  For irbesartan, the 90% confidence intervals (CIs) of AUC0-t, AUC0-∞, and Cmax were 103.27-116.71%, 105.01-121.47%, and 84.15-96.88%, respectively. For hydrochlorothiazide, the 90% CIs of AUC0-t, AUC0-∞, and Cmax were 96.11-109.02%, 95.15-107.35%, and 91.66-101.40%, respectively. A total of 3 mild AEs were reported in 3 subjects (12.5%).
  
  
  CONCLUSIONS
  In this study, a single dose (300/12.5-mg) of the test formulation of irbesartan and hydrochlorothiazide FDC tablet in fasting healthy Chinese male volunteers met WHO's and China's FDA regulatory criteria for assumption of bioequivalence to the reference formulation based on AUC and Cmax. Both formulations were well tolerated.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Lihua
authors.initials: L
authors.lastname: Wu
authors.forename: Xingjiang
authors.initials: X
authors.lastname: Hu
authors.forename: Guolan
authors.initials: G
authors.lastname: Wu
authors.forename: Yunliang
authors.initials: Y
authors.lastname: Zheng
authors.forename: Huili
authors.initials: H
authors.lastname: Zhou
authors.forename: You
authors.initials: Y
authors.lastname: Zhai
authors.forename: Meixiang
authors.initials: M
authors.lastname: Zhu
authors.forename: Jianzhong
authors.initials: J
authors.lastname: ShenTu
mesh_terms: D000284:Administration, Oral; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002681:China; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004338:Drug Combinations; D016568:Drugs, Generic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000077405:Irbesartan; D008297:Male; D008657:Metabolic Clearance Rate; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013777:Tetrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D004232:Diuretics; D004338:Drug Combinations; D016568:Drugs, Generic; D013607:Tablets; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D000077405:Irbesartan