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

The aim of this study was to determine the effects of probiotic bacteria and bile acids on the gliclazide permeability using in vitro Parallel Artificial Membrane Permeability Assay (PAMPA*) model, at three different pH values (5.8, 6.5 and 7.4).


There are significant interactions between probiotic bacteria and bile acids with gliclazide at the level of passive transport that could influence the bioavailability of this drug.


Probiotics are live microorganisms that represent the main dietary strategy for modulating the composition and metabolic activity of gut microbiota, which affects drug pharmacokinetics through its enzymatic activity. The high variability of human microbiota composition considerably contributes to the individually different responses to the same pharmacological therapy.\


Bile acids act as physiological surfactants in the process of digestion and absorption of lipids in the intestines. Additionally, these biomolecules have been shown to enhance intestinal permeability and bioavailability of both lipophilic and hydrophilic drugs. The outcome of bile acids on drug transport across the biological membrane depends on the type and the structure of the acids.\


The study showed that probiotic bacteria significantly increased the permeability of gliclazide across the PAMPA membrane at all observed pH values. However, the total amount of gliclazide during incubation with bacteria was significantly higher at lower pH compared to higher pH values. On the other hand, bile acids decreased the permeability of gliclazide through PAMPA membrane due to the creation of more stable complexes between them.\


These findings open the door to new studies that could provide patients with tailored treatments to diminish the differences caused by microbiota and bile acids.


PAMPA method is only suitable for examination of passive transport; future experiments should provide insight into interactions at the level of active transport.



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