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

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dc.article.number100491
dc.catalogadorvzp
dc.contributor.authorGarcía Alcalde, Mauricio Andrés
dc.contributor.authorHensler, Gonul
dc.contributor.authorAl Gousous, Jozef
dc.contributor.authorPielenhofer, Jonas
dc.contributor.authorWagner, Manfred
dc.contributor.authorLennernas, Hans
dc.contributor.authorLangguth, Petter
dc.date.accessioned2024-12-31T14:25:32Z
dc.date.available2024-12-31T14:25:32Z
dc.date.issued2023
dc.description.abstract© 2023 The Japanese Society for the Study of XenobioticsDrug 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.
dc.description.funderHumboldt Foundation
dc.description.funderAgencia Nacional de Investigación y Desarrollo
dc.format.extent10 páginas
dc.fuente.origenSIPA
dc.identifier.doi10.1016/j.dmpk.2023.100491
dc.identifier.eissn18800920
dc.identifier.issn18800920 13474367
dc.identifier.scopusidSCOPUS_ID:85148350928
dc.identifier.urihttps://www.jstage.jst.go.jp/browse/dmpk
dc.identifier.urihttps://doi.org/10.1016/j.dmpk.2023.100491
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/89418
dc.information.autorucEscuela de Química; Garcia Alcalde Mauricio Andres; S/I; 181066
dc.language.isoen
dc.nota.accesocontenido parcial
dc.publisherJapanese Society for the Study of Xenobiotics
dc.relation.ispartofDrug Metabolism and Pharmacokinetics
dc.revistaDrug Metabolism and Pharmacokinetics
dc.rightsacceso restringido
dc.subjectBioavailability
dc.subjectDrug absorption
dc.subjectDrug food interaction
dc.subjectDrug neutraceutical interaction
dc.subjectMucus encapsulation
dc.subjectPharmacokinetics
dc.subjectSystemic availability
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleNovel food drug interaction mechanism involving acyclovir, chitosan and endogenous mucus
dc.typeartículo
sipa.codpersvinculados181066
sipa.trazabilidadSCOPUS;02-03-2023
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