Pharmacokinetic and bioequivalence study comparing a fimasartan/rosuvastatin fixed-dose combination with the concomitant administration of fimasartan and rosuvastatin in healthy subjects.

Abstract

PurposeA new fixed-dose combination (FDC) formulation of 120 mg fimasartan and 20 mg rosuvastatin was developed to increase therapeutic convenience and improve treatment compliance.MethodsA randomized, open-label, single-dose, two-treatment, two-way crossover study with a 7-day washout period was conducted to compare the pharmacokinetic (PK) characteristics and bioequivalence between an FDC of fimasartan/rosuvastatin and the separate co-administration of fimasartan and rosuvastatin in healthy Korean volunteers. The plasma concentrations of fimasartan and rosuvastatin were analyzed by a validated liquid chromatography-tandem mass spectrometry method, for which serial blood samples were collected for up to 48 hours post-administration of fimasartan and 72 hours post-administration of rosuvastatin, in each period. The PK parameters were calculated using a non-compartmental method.ResultsA total of 78 subjects completed the study. All the 90% CIs of the geometric mean ratios (GMRs) fell within the predetermined acceptance range. The GMR and 90% CI for the area under the plasma concentration-time curve from time 0 to the last measurement (AUC0–t) and the maximum plasma concentration (Cmax) for fimasartan were 0.9999 (0.9391–1.0646) and 1.0399 (0.8665–1.2479), respectively. The GMR and 90% CI for the AUC0–t and Cmax for rosuvastatin were 1.0075 (0.9468–1.0722) and 1.0856 (0.9944–1.1852), respectively. Treatment with fimasartan and rosuvastatin was generally well tolerated without serious adverse events.ConclusionThe new FDC formulation of 120 mg fimasartan and 20 mg rosuvastatin can be substituted for the separate co-administration of fimasartan and rosuvastatin, for the advantage of better compliance with convenient therapeutic administration.