Purpose: Comorbid conditions of heart and liver disorders added to HCV-induced hepatic steatosis make co-administration of statins, and direct-acting antivirals is common in clinical practice. This study aimed to evaluate the pharmacokinetic interaction of atorvastatin and fixed-dose combination of sofosbuvir/ledipasvir "FDCSL" with rationalization to the underlying mechanism.
Methods: A randomized, three-phase crossover study that involves 12 healthy volunteers was performed. Participants received a single-dose of atorvastatin 80 mg alone, atorvastatin 80-mg plus tablets containing 400/90 mg FDCSL, or tablets containing 400/90 mg FDCSL alone. Plasma samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for atorvastatin, sofosbuvir, ledipasvir, and sofosbuvir metabolite "GS-331007," and their pharmacokinetics parameters were determined.
Results: Compared to atorvastatin alone, the administration of FDCSL caused a significant increase in both areas under the concentration-time curve from time zero to infinity (AUC0-∞) and maximum plasma concentration (Cmax) of atorvastatin by 65.5% and 156.0%, respectively. Also, atorvastatin caused a significant increase in the AUC0-∞ and Cmax of sofosbuvir by 32.0% and 11.0%, respectively. Similarly, AUC0-∞ and Cmax of sofosbuvir metabolite significantly increased by 84.0% and 74.0%, respectively. However, ledipasvir AUC0-∞ showed no significant change after atorvastatin intake. The elimination rate in all drugs revealed no significant changes.
Conclusion: After concurrent administration of FDCSL with atorvastatin, the AUC0-∞ of both atorvastatin and sofosbuvir were increased. Caution should be taken with close monitoring for possible side effects after co-administration of atorvastatin and FDCSL in clinical practice.
Keywords: Atorvastatin; GS-331007; Ledipasvir; P-glycoprotein; Pharmacokinetic interaction; Sofosbuvir.
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.