Purpose: A new fixed-dose combination (FDC) formulation of 120 mg fimasartan and 20 mg rosuvastatin was developed to increase therapeutic convenience and improve treatment compliance.
Methods: A 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.
Results: A 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.
Conclusion: The 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.
Keywords: bioequivalence; fimasartan; fixed-dose combination; pharmacokinetics; rosuvastatin.