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Drug Interchangeability of Generic and Brand Products of Fixed Dose Combination Tablets of Sofosbuvir and Ledipasvir (400/90 mg): Employment of Reference Scaled Average Bioequivalence Study on Healthy Egyptian Volunteers

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Abstract

Background and Objectives

The purpose of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence and to investigate the pharmacokinetic properties of two formulations of fixed dose combination (FDC) tablet of sofosbuvir (SOF) and ledipasvir (LED) (400/90 mg) in 36 healthy Egyptian volunteers.

Methods

The study was performed in single-dose, randomized-sequence, open-label, reference-replicated, 3-period crossover design (RTR, TRR, RRT), with a washout period of 2 weeks. A rapid and simple LC–MS/MS method was developed and validated for the simultaneous estimation of SOF and LED using eplerenone as an internal standard (IS).

Results

The results showed that the 90% confidence intervals (CIs) for natural log-transformed ratios of Cmax, AUClast and AUC∞ of SOF (89.95–115.31, 98.77–109.75 and 98.79–109.75) were within the RSABE acceptance limits. The 90% CIs for natural log-transformed ratios of Cmax and AUClast of LED (87.33–115.15 and 83.82–112.26) were within the FDA bioequivalence limits (80.00–125.00). In addition, the in vitro dissolution study was done and both formulations released > 85% of drug within 15 min in the proposed dissolution medium.

Conclusions

In conclusion, bioequivalence between the two fixed-dose combination products was demonstrated for both active ingredients.

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Acknowledgements

Authors would like to acknowledge Advanced Research Center (ARC), Egypt, for supporting this research and providing the facilities for completing this work.

Author information

Authors and Affiliations

  1. Clinical Pharmacy Department, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt, Cairo, Egypt

    Ehab Rasmy Bendas

  2. Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt

    Mamdouh R. Rezk

  3. Department of Pharmaceutics, Faculty of Pharmacy, Deraya University, Minya, Egypt

    Kamal A. Badr

  4. Advanced Research Center (ARC), Nasr City, Cairo, Egypt

    Kamal A. Badr

Authors
  1. Ehab Rasmy Bendas
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  2. Mamdouh R. Rezk
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  3. Kamal A. Badr
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Contributions

ERB and MRR conceived and designed the study. KAB supervised and managed the clinical procedures. MRR developed, validated and supervised the analytical procedures during the study. ERB was responsible for pharmacokinetic and statistical analysis. All authors participated in writing and reviewing the manuscript. All authors have read and approved the final version of the manuscript.

Corresponding author

Correspondence to Ehab Rasmy Bendas.

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Funding

This work was supported by Advanced Research Center (ARC), Egypt. All chemicals, reagents and solvents; whole analytical instruments and all clinical facilities were supplied by ARC.

Conflict of interest

Ehab R. Bendas, Mamdouh R. Rezk and Kamal A. Badr declare that there is no conflict of interests in this study.

Ethics approval

Ethics committee of Advanced Research Center approved the protocol of the clinical trial. All procedures in this study were in accordance with the 1964 Helsinki declaration.

Informed consent

All volunteers provided written informed consent before receiving study medications or subjected to any test procedures.

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Bendas, E.R., Rezk, M.R. & Badr, K.A. Drug Interchangeability of Generic and Brand Products of Fixed Dose Combination Tablets of Sofosbuvir and Ledipasvir (400/90 mg): Employment of Reference Scaled Average Bioequivalence Study on Healthy Egyptian Volunteers. Clin Drug Investig 38, 439–448 (2018). https://doi.org/10.1007/s40261-018-0622-8

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  • DOI: https://doi.org/10.1007/s40261-018-0622-8

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