Pharmacokinetic drug interaction study using fimasartan and rosuvastatin in healthy volunteers

Objective: This study evaluated the possible pharmacokinetic interactions between rosuvastatin and fimasartan, an angiotensin II type 1 (AT1) receptor blocker (ARB), approved in Korea for the treatment of mild to moderate hypertension. Methods: In this open-label, multiple-dose, two-period, single-sequence study, the enrolled subjects were randomized into two separate parts (A and B). In part A, subjects received 120 mg of fimasartan alone for 7 days during period I, and 120 mg fimasartan with 20 mg rosuvastatin for 7 days during period II. In Part B, subjects received rosuvastatin alone, followed by concomitant administration of fimasartan, with the same doses used as in Part A. There was a 7-day washout between periods I and II. Serial blood samples were collected for up to 48 hours for fimasartan and for up to 72 hours for rosuvastatin after the last dose of each period to determine the steady-state pharmacokinetics of both drugs. Results: The mean C-max,C-ss and AUC(tau,ss) values of fimasartan were 258.03 +/- 176.75 ng/mL and 746.52 +/- 273.49 ngxh/mL for fimasartan alone, and 289.40 +/- 231.44 ng/mL and 848.43 +/- 267.45 ngxh/mL for fimasartan and rosuvastatin co-administration, respectively (p-values for C-max,C-ss and AUC(tau,ss), 0. 513 and 0.006, respectively). The mean C-max,C-ss and AUC(tau,ss) values of rosuvastatin were 9.94 +/- 4.48 ng/mL and 85.29 +/- 36.25 ngxh/mL for rosuvastatin alone and 11.94 +/- 8.47 ng/mL and 77.33 +/- 38.71 ngxh/mL for fimasartan and rosuvastatin coadministration, respectively (p-values for C-max,C-ss and AUC(tau,ss) 0.066 and 0.009, respectively). The geometric mean ratio (GMR) and 90% confidence intervals (CI) for the C-max,C-ss and AUC(tau,ss) of fimasartan (with/without rosuvastatin) were 1.109 (0.813 - 1.511) and 1.159 (1.061 - 1.265), respectively. The GMR and 90% CI for the C-max,C-ss and AUC(tau,ss) of rosuvastatin (with/without fimasartan) were 1.090 (0.979 - 1.213) and 0.870 (0.804 - 0.940), respectively. Conclusions: These results suggest that fimasartan and rosuvastatin have no relevant pharmacokinetic drug-drug interactions. All treatments were well tolerated during this study, with no serious adverse effects.