The relative bioavailability of 2 prototype fixed-dose combination formulations for amlodipine and rosuvastatin in healthy white and Chinese subjects

Clin Pharmacol Drug Dev. 2016 Mar;5(2):131-40. doi: 10.1002/cpdd.214. Epub 2015 Oct 5.

Abstract

A fixed-dose combination (FDC) may improve patient compliance and clinical outcomes in the management of cardiovascular risk in hypertensive and dyslipidemic patients. The study (NCT02075619) evaluated the bioavailability of 2 prototype FDC tablet formulations (FDC1 and FDC2) of amlodipine/rosuvastatin (10 mg/20 mg) compared with coadministered reference tablets. It was a randomized, single-dose, 3-way crossover pilot study in healthy white (n = 12) and Chinese (n = 12) adults. Three treatments (FDC1, FDC2, and reference) were administered after fasting with a washout period of 12-17 days. The pharmacokinetics of amlodipine and rosuvastatin were studied for all subjects (pooled) and by ethnicity. Safety and tolerability were also evaluated. Both FDCs met the bioequivalence criteria (90% confidence intervals falling within the range of 0.80-1.25) for AUC0-t and Cmax for amlodipine and rosuvastatin. Intrasubject variability (AUC0-t and Cmax ) was in the region of 23%-25% for rosuvastatin and 7%-10% for amlodipine. The FDC formulations demonstrated similar bioavailability to coadministered commercially available amlodipine and rosuvastatin. All treatments were generally well tolerated.

Keywords: amlodipine; bioavailability; fixed-dose combination; pharmacokinetics; rosuvastatin.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Amlodipine / administration & dosage*
  • Amlodipine / pharmacokinetics
  • Anticholesteremic Agents / administration & dosage*
  • Anticholesteremic Agents / pharmacokinetics
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / pharmacokinetics
  • Area Under Curve
  • Asian People
  • Biological Availability
  • Cross-Over Studies
  • Drug Combinations
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Rosuvastatin Calcium / administration & dosage*
  • Rosuvastatin Calcium / pharmacokinetics
  • Tablets
  • Therapeutic Equivalency
  • White People
  • Young Adult

Substances

  • Anticholesteremic Agents
  • Antihypertensive Agents
  • Drug Combinations
  • Tablets
  • Amlodipine
  • Rosuvastatin Calcium