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Pharmacokinetic interaction between atorvastatin and fixed-dose combination of sofosbuvir/ledipasvir in healthy male Egyptian volunteers

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

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.

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Acknowledgements

Authors thank the members of the Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University.

Data availability (data transparency)

The datasets generated during and/or analyzed during the current study are not publicly available due to confidentiality reasons but are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, Faculty of Pharmacy, Kafrelsheikh University, Kafr El-Sheikh, 33511, Egypt

    H. A. Elmekawy, K. S. Abdelkawy & A. A. Ali

  2. Department of Analytical Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura, 35516, Egypt

    F. Belal

  3. Department of Pharmaceutical Technology, Faculty of Pharmacy, Kafrelsheikh University, Kafr El-Sheikh, Egypt

    A. E. Abdelaziz

  4. Pacific University Oregon School of Pharmacy, Hillsboro, OR, 97123, USA

    F. Elbarbry

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  1. H. A. Elmekawy
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  3. A. E. Abdelaziz
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  4. K. S. Abdelkawy
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  5. A. A. Ali
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Contributions

Conceptualization: FE, HE, and KA

Methodology: HE, FB, KA, and AEA

Validation: FE, FB, AAA, and KA

Formal analysis: FE, HE, AEA, and AAA

Investigation: FE, HE, and KA

Resources: FE, HE, and KA

Data curation: FE, HE, KA, AEA, and AAA

Writing—original draft preparation: HE, KA, and FE

Writing—review and editing: FE, HE, KA, AEA, and AAA

Supervision: FE, KA

Project administration: KA, HE, and FE

All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to F. Elbarbry.

Ethics declarations

Ethical approval

The study protocol was approved by the ethics committee of Kafrelsheikh University in accordance with the Declaration of Helsinki and its amendments.

Informed consent

All subjects provided written informed consent before participation.

Consent for publication

Patients expressed no objection for the publication of the results.

Conflict of interest

The authors declare no competing interests.

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Key points

• Atorvastatin increases the extent of absorption of sofosbuvir and its metabolite (GS-331007) without affecting ledipasvir pharmacokinetics.

• Atorvastatin AUC0−∞ and Cmax increased after FDCSL intake.

• Patients should take caution about atorvastatin and sofosbuvir side effects.

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Elmekawy, H.A., Belal, F., Abdelaziz, A.E. et al. Pharmacokinetic interaction between atorvastatin and fixed-dose combination of sofosbuvir/ledipasvir in healthy male Egyptian volunteers. Eur J Clin Pharmacol 77, 1369–1379 (2021). https://doi.org/10.1007/s00228-021-03130-z

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