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- Garcia, Mauricio A., et al.
(författare)
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Novel food drug interaction mechanism involving acyclovir, chitosan and endogenous mucus
- 2023
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Ingår i: Drug Metabolism and Pharmacokinetics. - : Elsevier. - 1347-4367 .- 1880-0920. ; 49
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Tidskriftsartikel (refereegranskat)abstract
- 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 chi-tosan 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.(c) 2023 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.
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- Nakayama, Noboru, et al.
(författare)
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Developments of mass spectrometry-based technologies for effective drug development linked with clinical proteomes.
- 2016
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Ingår i: Drug Metabolism and Pharmacokinetics. - : Elsevier BV. - 1347-4367. ; 31:1, s. 3-11
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Forskningsöversikt (refereegranskat)abstract
- A strong demand in drug discovery and development today is to overcome "Big Gaps" encountered by differences in species and races, to accelerate effective developments in cost and time, and to meet medical needs. Moreover, drugs of various types have emerged which cover middle-size molecules and polymers rather than conventional small molecules. Upon those challenges, mass spectrometry (MS)-based technologies, which will be described in this paper, will play an increasingly important role, among which the liquid chromatography-tandem mass spectrometry (LC/MS/MS) platform will be powerful as rapid and molecule-based analysis more than ever. nanoPore Optical Interferometry (nPOI) newly introduced can detect even weak interactions in protein-protein and protein-compound, and can be connected directly to LC/MS/MS for identification of binding molecular species, which will be quite useful for affinity ranking and high-throughput interaction screening. Imaging MS provides the molecular information and spatial distribution of targeted molecules within a tissue specimen. MS-based clinical proteomics utilizing clinical specimens and empowered by advanced bioinformatics can attain both key protein-protein interaction (PPI) networks with major protein players responsible for functional mechanisms of a disease subtype. An integration of those MS-based technologies will deliver a seamless platform of drug development from molecules identified in human clinical specimens.
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