PAMPA model of gliclazide permeability: The impact of probiotic bacteria and bile acids

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NSTL
Elsevier

外文摘要：Gut microbiota and bile acids possess the ability to modify absorption and pharmacokinetic profile of numerous drugs. Since the variability of gliclazide response in patients cannot be explained only by genetic factors, the influence of gut microbiota and bile acids should be considered. The aim of this study was to determine the effects of probiotic bacteria and bile acids on the gliclazide permeability. The permeability of gliclazide with and without probiotic bacteria and bile acids (cholic acid, CA and deoxycholic acid, DCA) was tested using in vitro PAMPA model, at three different pH values (5.8, 6.5 and 7.4). Concentrations of gliclazide were determined by HPLC analysis. The interactions of gliclazide and bile acids were also investigated by molecular mechanics calculations (MM2). Probiotic bacteria significantly increased the permeability of gliclazide across the PAMPA membrane at all observed pH values while the total amount of gliclazide during incubation with bacteria was significantly reduced at pH 7.4, which could be a consequence of partial metabolism of the drug by enzymes of probiotic bacteria. Bile acids decreased the permeability of gliclazide through PAMPA membrane, with more pronounced effects of DCA, by forming more stable complexes with gliclazide. Given that probiotic bacteria and bile acids are naturally present in the gut and that each individual has a specific bacterial fingerprint, future research should extend the explanation of their effect on the gliclazide bioavailability and therapy individualization in in vivo conditions.

外文关键词：

PAMPAgliclazidedrug absorptionbile acidsgut microflora

作者：

Danic, Maja、Pavlovic, Nebojsa、Stanimirov, Bojan、Lazarevic, Slavica、Vukmirovic, Sasa、Al-Salami, Hani、Mikov, Momir

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作者单位：

Univ Novi Sad, Fac Med, Dept Pharmacol Toxicol & Clin Pharmacol, Hajduk Veljkova 3, Novi Sad

Univ Novi Sad, Fac Med, Dept Pharm, Hajduk Veljkova 3, Novi Sad, Vojvodina, Serbia

Univ Novi Sad, Fac Med, Dept Biochem, Hajduk Veljkova 3, Novi Sad, Vojvodina, Serbia

Curtin Univ, Curtin Hlth Innovat Res Inst, Sch Pharm & Biomed Sci, Biotechnol & Drug Dev Res Lab

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出版年：

2021

DOI：

10.1016/j.ejps.2020.105668

European journal of pharmaceutical sciences

ISTP

ISSN：0928-0987

年,卷(期)：2021.158

被引量5
参考文献量46