title: Pharmacokinetics of single and multiple oral doses of valsartan/amlodipine (80/5 mg) in healthy Chinese subjects.
abstract: OBJECTIVE
  The efficacy and safety of valsartan/amlodipine combination have been demonstrated for the treatment of hypertension. In China, where the prevalence of hypertension is increasing the pharmacokinetic study of valsartan, amlodipine assumes significance. The aim of this study was to characterize the pharmacokinetics (PK) of valsartan and amlodipine following single- and multiple-dose oral administrations of valsartan/ amlodipine 80/5 mg fixed-dose combination in healthy Chinese subjects.
  
  
  METHODS
  This was an open-label, two-period (single-dose treatment followed by a multiple-dose (once-daily for 9 days), with a 7-day intertreatment washout period) study conducted in 18 subjects. Serial blood samples were collected at pre-defined time points, and the plasma concentrations of valsartan and amlodipine were measured using LC-MS/MS. Safety was evaluated after single- and multiple-dose drug administration.
  
  
  RESULTS
  Following the single-dose oral administration of valsartan/amlodipine 80/5 mg, valsartan and amlodipine plasma concentrations reached peak levels at median tmax of 3 and 6 h, respectively. These concentrations declined thereafter, with mean elimination half-lives of 7.7 h (single dose) and 8.6 h (multiple dose) for valsartan, and 47 h (single dose) and 45 h (multiple dose) for amlodipine. After a 9-day multiple-dose treatment (at steady state), accumulation of valsartan and amlodipine was consistent with their half-lives. The single- and multiple-dose administration of valsartan/amlodipine 80/5 mg was associated with asymptomatic hypotension, consistent with the pharmacological activity of the combination of these two blood pressure-lowering drugs when co-administered in healthy subjects.
  
  
  CONCLUSIONS
  The PK of valsartan and amlodipine are linear following oral administration of valsartan/amlodipine fixed-dose combination.
authors.affiliation: Pharmacy Department, Peking University Third Hospital, Beijing, China.
authors.forename: Jingli
authors.initials: J
authors.lastname: Duan
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.forename: Qi
authors.initials: Q
authors.lastname: Yin
authors.forename: Rajesh
authors.initials: R
authors.lastname: Karan
authors.forename: Karin
authors.initials: K
authors.lastname: Meiser
authors.forename: Harold Tom
authors.initials: HT
authors.lastname: Smith
authors.forename: Gangadhar
authors.initials: G
authors.lastname: Sunkara
mesh_terms: D060433:Administration, Ophthalmic; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D017311:Amlodipine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000068838:Amlodipine, Valsartan Drug Combination; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002681:China; D002853:Chromatography, Liquid; D004338:Drug Combinations; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D053719:Tandem Mass Spectrometry; D013777:Tetrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000068838:Amlodipine, Valsartan Drug Combination; D000959:Antihypertensive Agents; D004338:Drug Combinations; D013777:Tetrazoles; D017311:Amlodipine