title: The relative bioavailability of 2 prototype fixed-dose combination formulations for amlodipine and rosuvastatin in healthy white and Chinese subjects.
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.
authors.affiliation: Institute of Chemical and Engineering Sciences (ICES), Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Htar H
authors.initials: HH
authors.lastname: Nwe
authors.affiliation: GlaxoSmithKline, Stevenage, United Kingdom.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Bullman
authors.affiliation: GlaxoSmithKline, Bangalore, India.
authors.forename: Shashidhar M
authors.initials: SM
authors.lastname: Joshi
authors.affiliation: GlaxoSmithKline, Stevenage, United Kingdom.
authors.forename: Annie
authors.initials: A
authors.lastname: Stylianou
authors.affiliation: GlaxoSmithKline, Singapore.
authors.forename: Shiva G
authors.initials: SG
authors.lastname: Kapsi
mesh_terms: D000328:Adult; D017311:Amlodipine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D044466:Asian People; D001682:Biological Availability; D018592:Cross-Over Studies; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013607:Tablets; D013810:Therapeutic Equivalency; D044465:White People; D055815:Young Adult
chemical_list: D000924:Anticholesteremic Agents; D000959:Antihypertensive Agents; D004338:Drug Combinations; D013607:Tablets; D017311:Amlodipine; D000068718:Rosuvastatin Calcium
keywords: amlodipine; bioavailability; fixed-dose combination; pharmacokinetics; rosuvastatin