Drug Res (Stuttg) 2022; 72(06): 319-326
DOI: 10.1055/a-1835-1690
Original Article

Statins Increase the Bioavailability of Fixed-Dose Combination of Sofosbuvir/Ledipasvir by Inhibition of P-glycoprotein

K.S. Abdelkawy
1   Department of Clinical Pharmacy, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt
Fathalla Belal
2   Department of Analytical Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura, Egypt
AbdelazizE Abdelaziz
3   Department of Pharmaceutical Technology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt
H. A. Elmekawy
1   Department of Clinical Pharmacy, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt
M. Y. Abdelgaied
4   Department of Pharmacology, Toxicology and Clinical Pharmacy, Faculty of Pharmacy and Biotechnology, German University in Cairo, Egypt
N. M. El-Khodary
1   Department of Clinical Pharmacy, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt
› Author Affiliations
Funding This work was supported by the Research Center of Clinical Pharmacy, Faculty of Pharmacy, Kafrelsheikh University, Egypt.


Background Coadministration of statins and direct acting antiviral agents is frequently used. This study explored the effects of both atorvastatin and lovastatin on pharmacokinetics of a fixed-dose combination of sofosbuvir/ledipasvir “FDCSL”.

Methods 12 healthy volunteers participated in a randomized, three-phase crossover trial and were administered a single atorvastatin dose 80 mg plus tablet containing 400/90 mg FDCSL, a single lovastatin dose 40 mg plus tablet containing 400/90 mg FDCSL, or tablets containing 400/90 mg FDCSL alone. Liquid chromatography-tandem mass spectrometry was used to analyze plasma samples of sofosbuvir, ledipasvir and sofosbuvir metabolite “GS-331007” and their pharmacokinetic parameters were determined.

Results Atorvastatin caused a significant rise in sofosbuvir bioavailability as explained by increasing in AUC0−∞ and Cmax by 34.36% and 11.97%, respectively. In addition, AUC0-∞ and Cmax of GS-331007 were increased by 73.73% and 67.86%, respectively after atorvastatin intake. Similarly, co-administration of lovastatin with FDCSL increased the bioavailability of sofosbuvir, its metabolite (AUC0-∞ increase by 17.2%, 17.38%, respectively, and Cmax increase by 12.03%, 22.24%, respectively). However, neither atorvastatin nor lovastatin showed a change in ledipasvir bioavailability. Hepatic elimination was not affected after statin intake with FDCSL. Compared to lovastatin, atorvastatin showed significant increase in AUC0-∞ and Cmax of both sofosbuvir and its metabolite.

Conclusions Both atorvastatin and lovastatin increased AUC of sofosbuvir and its metabolite after concurrent administration with FDCSL. Statins’ P-glycoprotein inhibition is the attributed mechanism of interaction. The increase in sofosbuvir bioavailability was more pronounced after atorvastatin intake. Close monitoring is needed after co-administration of atorvastatin and FDCSL.

Publication History

Received: 07 February 2022

Accepted: 19 April 2022

Article published online:
20 June 2022

© 2022. Thieme. All rights reserved.

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