title: Comparisons of the pharmacokinetics and tolerability of fixed-dose combinations of amlodipine besylate/losartan and amlodipine camsylate/losartan in healthy subjects: a randomized, open-label, single-dose, two-period, two-sequence crossover study.
abstract: BACKGROUND
  A fixed-dose combination (FDC) of amlodipine and losartan has been used to reduce blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The aim of this study was to evaluate the pharmacokinetic (PK) characteristics and tolerability of an FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium compared to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium in healthy subjects.
  
  
  METHODS
  A randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted on 46 healthy male subjects. Blood concentrations were measured by liquid chromatography-tandem mass spectrometry. Blood samples were collected up to 144 hours post dose for each period. PK parameters were calculated in each treatment group using a noncompartmental method. The 90% confidence intervals (CIs) of the geometric mean ratios of the two treatments for the maximum plasma concentration (Cmax) and the area under the concentration curve from time zero to the last quantifiable time point (AUC0-t) were estimated. Tolerability assessments were performed for all subjects who received the drug at least once.
  
  
  RESULTS
  The PK profiles of the two treatments were similar. For amlodipine, the geometric mean ratios (90% CIs) of amlodipine besylate to amlodipine camsylate for theCmaxand AUC0-twere 0.98 (0.94-1.01) and 0.97 (0.93-1.01), respectively. The corresponding values for losartan were 0.91 (0.81-1.02) and 1.05 (0.98-1.12), respectively. The incidence of adverse events was not significantly different between the two treatments, and both were well tolerated.
  
  
  CONCLUSIONS
  An FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium produced similar results to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium treatment with respect to the PK parameters of amlodipine and losartan based onCmaxand AUC0-tvalues. The amlodipine besylate/losartan potassium combination was well tolerated by healthy male subjects.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine.
authors.forename: YoonJung
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Clinical Trials Center, Seoul National University Hospital.
authors.forename: SeungHwan
authors.initials: S
authors.lastname: Lee
authors.affiliation: Research Institute.
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Cho
authors.affiliation: Research Institute.
authors.forename: Won-Ho
authors.initials: WH
authors.lastname: Kang
authors.affiliation: Global R&D, Korea United Pharm Inc., Seoul, Republic of Korea.
authors.forename: Kyu-Yeol
authors.initials: KY
authors.lastname: Nam
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine.
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Jang
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine.
authors.forename: Kyung-Sang
authors.initials: KS
authors.lastname: Yu
mesh_terms: D000284:Administration, Oral; D017311:Amlodipine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D019808:Losartan / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D017311:Amlodipine; D019808:Losartan
keywords: amlodipine; comparative pharmacokinetics; drug development; losartan