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Investigation of the effect of verapamil on the regional absorption of sofosbuvir from rabbit intestine in situ

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Abstract

Purpose

Sofosbuvir, a nucleotide antiviral drug, is a Biopharmaceutics Classification System (BCS) class III prodrug suffering from limited intestinal absorption due to its high hydrophilicity and low intestinal permeability. This research aims to investigate the luminal stability of Sofosbuvir, the influence of anatomical site on its intestinal absorption and the effects of verapamil on such absorption.

Method

The study utilized in situ rabbit intestinal perfusion technique to examine absorption of Sofosbuvir from duodenum, jejunum, ileum and ascending colon. This was conducted both with and without verapamil.

Results

The luminal stability study showed that Sofosbuvir was subjected to premature degradation with varying fractions degraded from the different intestinal segments. The in situ perfusion data showed incomplete absorption of Sofosbuvir from small and large intestinal segments. The recorded values of the absorptive clearance per unit length (Pe.A/L) of Sofosbuvir were 0.026, 0.0075, 0.0026, & 0.054 ml/min.cm for duodenum, jejunum, ileum, and ascending colon, respectively. The Pe.A/L values were ordered as colon > duodenum > jejunum > ileum. This is the opposite rank of P-gp content in the different intestinal segments. The recorded values of the length required for complete Sofosbuvir absorption (L95%) were 29.58, 128.47, 949.2 and, 13.63 cm for duodenum, jejunum, ileum, and ascending colon, respectively. Co-perfusion with verapamil significantly increased Pe.A/L and reduced the L95% of Sofosbuvir from both jejunum and ileum (P-value < 0.05).

Conclusion

The results indicated that the absorptive clearance of Sofosbuvir was site dependent and associated with the content of P-glycoprotein, in addition to the expected drug interactions that can occur in polymedicated hepatitis C virus (HCV) infected patients.

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Data availability

All authors are sure that all data and materials support our published claims and comply with field standards. And all listed authors have approved the manuscript before submission, including the names and order of authors.

Ethical approval.

Animal handling and the study treatments were performed according to the permission of the Ethical Committee of College of Pharmacy, Tanta University (Approval number, 108017).

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Funding

No funding was received for conducting this study.

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Tanta, Tanta, 31111, Egypt

    Nada M. Mohsen, Esmat E. Zein El-Din, Mohamed A. Osman & Shimaa M. Ashmawy

  2. Department of Pharmaceutics, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt

    Esmat E. Zein El-Din

Authors
  1. Nada M. Mohsen
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  2. Esmat E. Zein El-Din
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  3. Mohamed A. Osman
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  4. Shimaa M. Ashmawy
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Contributions

Nada M. Mohsen: Investigation, Data curation and Writing drafted manuscript. Esmat E. Zein El-Din: Visualization, Supervision, Writing, Reviewing and Editing. Mohamed A. Osman: Conceptualization, Methodology, Data curation, Visualization and Supervision. Shimaa M. Ashmawy: Data Curation, Visualization, Writing, Reviewing and Editing.

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Correspondence to Shimaa M. Ashmawy.

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Mohsen, N.M., El-Din, E.E.Z., Osman, M.A. et al. Investigation of the effect of verapamil on the regional absorption of sofosbuvir from rabbit intestine in situ. DARU J Pharm Sci 30, 49–58 (2022). https://doi.org/10.1007/s40199-021-00429-1

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