Novel food drug interaction mechanism involving acyclovir, chitosan and endogeno...

연구 요약

Novel food drug interaction mechanism involving acyclovir, chitosan and endogenous mucus.

Drug metabolism and pharmacokinetics 학술지에 발표된 이 연구는 García MA, Hensler G, Al-Gousous J 외 연구팀이 수행하였습니다.

이 연구는 'Novel food drug interaction mechanism involving acyclovir, chitosan and endogenous mucus.'에 대한 과학적 분석을 제공합니다.

핵심 내용

Drug absorption from drug products may be affected by pharmaceutical excipients and/or food additives through different mechanisms. Chitosan is a recognized nutraceutical, with potential as an excipient due to its permeability enhancer properties. While chitosan properties have been evaluated in in vitro and pre-clinical models, studies in humans are scarce. Unexpectedly, a controlled clinical trial showed chitosan actually reduced acyclovir bioavailability. The effect seems to be related to an interaction with gastrointestinal mucus that prevents further absorption, although more in depth research is needed to unravel the mechanism. In this paper, we propose a mechanism underlying this excipient effect. The mucus - chitosan interaction was characterized and its effect on acyclovir diffusion, permeation and bioaccessibility was investigated. Further, pharmacokinetic modeling was used to assess the clinical relevance of our findings. Results suggest that in situ coacervation between endogenous mucus and chitosan rapidly entrap 20-30% of acyclovir dissolved dose in the intestinal lumen. This local reduction of acyclovir concentration together with its short absorption window in the small intestine would explain the reduction in acyclovir Cmax and AUC. This study highlights the importance of considering mucus in any biorelevant absorption model attempting to anticipate the effect of chitosan on drug absorption.

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