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The Interesting Case of Acyclovir Delivered Using Chitosan in Humans: Is it a Drug Issue or Formulation Issue?

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ABSTRACT

Purpose

Attempts to formulate acyclovir to improve its bioavailability and reduce the frequency of dosing from the present q4h have not materialized.

Discussion

It was thought that an approach using permeability enhancer such as chitosan may impart improved absorption profile to acyclovir; however, the recently published pharmacokinetic data suggested otherwise. The lack of promise of chitosan formulation was attributed to the muco-adhesive properties of chitosan to hold off acyclovir and preventing its transport across the gastrointestinal tract. However, the above hypothesis was refuted by another published human pharmacokinetic study of fexofenadine formulated with chitosan formulation - in this work it was unambiguously shown that chitosan helped in enhanced absorption of fexofenadine which is a well-known Pgp substrate. If one examines the pharmacokinetic disposition of acyclovir, it is clear that renal elimination is so rapid necessitating frequent dosing of acyclovir. In summary, the ability of chitosan based formulations to aid in the oral absorption of drugs may be drug dependent as enumerated by data obtained from acyclovir and fexofenadine. While chitosan favourably improved the pharmacokinetics of fexofenadine, acyclovir may not be ideal for chitosan type of formulation.

Conclusion

The choice of the drug and the formulation type intended to deliver the drug need to be made in a diligent and pragmatic fashion.

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Abbreviations

ACR:

Acyclovir

AUC:

Area under the plasma concentration versus time curve

Cmax :

Peak plasma concentration

DNA:

Deoxyribonucleic acid

h:

Hours

HCl:

Hydrochloride

Pgp:

P-glycoprotein

q4h:

Once every 4 hours

Tmax :

Time to peak plasma concentration

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ACKNOWLEDGMENTS AND DISCLOSURES

The author has no conflict of interest to declare in the contents of the manuscript.

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  1. Suramus Bio, Drug Development, J.P. Nagar I Phase, Bangalore, 560078, Karnataka, India

    Nuggehally R. Srinivas

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  1. Nuggehally R. Srinivas
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Srinivas, N.R. The Interesting Case of Acyclovir Delivered Using Chitosan in Humans: Is it a Drug Issue or Formulation Issue?. Pharm Res 33, 543–547 (2016). https://doi.org/10.1007/s11095-015-1811-2

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