Pharmacokinetic interaction between fimasartan and atorvastatin in healthy male volunteers

Introduction: Major cardiovascular risk factors, including hypertension and dyslipidemia, are often comorbidities, frequently leading to concurrent prescription of angiotensin receptor blockers and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins). The study's objective was to evaluate the effect of coadministration of fimasartan and atorvastatin on their pharmacokinetics (PKs). Subjects and methods: In a randomized, open-label, three-period, six-sequence, crossover, multiple-dose study, 36 healthy subjects received 120 mg fimasartan, 40 mg atorvastatin, or both (based on their assigned sequence) once daily for 7 days in each period, with a 7-day washout between periods. Blood samples for the PK analysis of fimasartan, atorvastatin, and the 2-hydroxy atorvastatin metabolite were collected up to 48 h after the last dose. Results: The coadministration of fimasartan and atorvastatin was well tolerated and led to an increase in the peak concentration and area under the concentration-time curve at steady state of fimasartan by 2.18-fold (95% confidence interval [CI], 1.79-2.65) and 1.35-fold (95% CI, 1.26-1.43) and those of atorvastatin increased by 1.82-fold (95% CI, 1.51-2.18) and 1.12-fold (95% CI, 1.04-1.22), respectively. Conclusion: Coadministration increased the systemic exposures of fimasartan and atorvastatin, but the clinical significance of this finding needs to be evaluated with respect to exposure responses and clinical outcomes.