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 Cmax,ssand AUCτ,ssvalues of fimasartan were 258.03 ± 176.75 ng/mL and 746.52 ± 273.49 ng×h/mL for fimasartan alone, and 289.40 ± 231.44 ng/mL and 848.43 ± 267.45 ng×h/mL for fimasartan and rosuvastatin coadministration, respectively (p-values for Cmax,ssand AUCτ,ss, 0. 513 and 0.006, respectively). The mean Cmax,ssand AUCτ,ssvalues of rosuvastatin were 9.94 ± 4.48 ng/mL and 85.29 ± 36.25 ng×h/mL for rosuvastatin alone and 11.94 ± 8.47 ng/mL and 77.33 ± 38.71 ng×h/mL for fimasartan and rosuvastatin coadministration, respectively (p-values for Cmax,ssand AUCτ,ss, 0.066 and 0.009, respectively). The geometric mean ratio (GMR) and 90% confidence intervals (CI) for the Cmax,ssand AUCτ,ssof 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 Cmax,ssand AUCτ,ssof 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. .
Woo Youl
WY
Kang
Eun Hee
EH
Kim
Sook Jin
SJ
Seong
Mi-Ri
MR
Gwon
Dong Heon
DH
Yang
Hyun-Ju
HJ
Kim
Mi-Sun
MS
Lim
Hae Won
HW
Lee
Young-Ran
YR
Yoon
D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001713:Biphenyl Compounds / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D004347:Drug Interactions; D064368:Healthy Volunteers; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D000068718:Rosuvastatin Calcium / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D013777:Tetrazoles / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013777:Tetrazoles; D000068718:Rosuvastatin Calcium; C558933:fimasartan