中国P站

P-glycoprotein; Antiviral drugs; Oral absorption; Drug efflux; Bioavailability; Drug transporters; Pharmacokinetics; Multidrug resistance; Intestinal barriers; Clinical pharmacology

Introduction

Oral administration remains the most convenient and preferred route for antiviral therapy. However, many antiviral agents exhibit suboptimal oral bioavailability due to poor permeability or active efflux by intestinal transporters. P-glycoprotein (P-gp), a membrane-bound efflux transporter encoded by the ABCB1 gene, is highly expressed in the gastrointestinal tract and plays a critical role in limiting drug absorption [1-5]. It recognizes a broad range of structurally diverse compounds and actively transports them out of cells, reducing systemic exposure. Several clinically used antiviral drugs—such as ritonavir, lopinavir, and acyclovir—are known P-gp substrates. This review discusses the clinical significance of P-gp-mediated drug efflux and strategies to overcome these limitations to improve antiviral therapy [6-10].

Discussion

The presence of P-gp in enterocytes significantly affects the pharmacokinetic profiles of orally administered antivirals by reducing their absorption and increasing variability. Inhibiting P-gp function or bypassing its recognition has been proposed to enhance bioavailability. Co-administration with P-gp inhibitors like verapamil or cyclosporine A can improve plasma concentrations but may pose safety concerns. Structural modifications to reduce efflux liability or utilizing nanoparticle carriers can also enhance absorption. Pharmacogenetic variations in the ABCB1 gene (e.g., C3435T) affect P-gp expression and activity, contributing to interindividual variability in drug response. Clinical studies highlight the need for considering P-gp interactions in antiviral therapy, especially in co-treatment settings involving HIV, hepatitis, or COVID-19. Regulatory guidelines now require transporter studies during drug development to identify potential P-gp-mediated interactions.

Conclusion

P-glycoprotein significantly influences the oral absorption and clinical effectiveness of antiviral drugs. Understanding its role and integrating strategies to circumvent its action are crucial for optimizing antiviral therapy. Future research should focus on transporter profiling during drug design and exploring safe modulation techniques to enhance therapeutic outcomes.

References

1. Amado RG, Wolf M, Peeters M (2008) . J Clin Oncol 26: 1626-1634.

   , ,

2. Apperley JF (2007) Lancet Oncol 8: 1018-1029.

   , ,

3. Bertilsson L, Dengler HJ, Eichelbaum M (1980) . Eur J Clin Pharmacol 17: 153-155.

   , ,

4. Beutler E, Gelbart T, Demina A (1998) Proc Natl Acad Sci U S A 95: 8170-8174.

   , ,

5. Bosch TM, Meijerman I, Beijnen JH (2006) . Clin Pharmacokinet 45: 253-285.

   , ,

6. Bosma PJ, Chowdhury JR, Bakker C (1995) N Engl J Med 333: 1171-1175.

   , ,

7. Camilleri M, Saito YA (2008) Methods Mol Biol 448: 395-412.

   , ,

8. Carbonell Sala S, Brandi ML (2007) J Endocrinol Invest 30: 2-7.

   ,

9. Carson PE, Flanagan CL, Ickes CE (1956) Science 124: 484-485.

   ,

10. Chowbay B, Li H, David M (2005) Br J Clin Pharmacol 60: 159-171.

    , ,