Gliclazide, a second-generation sulfonylurea derivative still widely used as a second-line treatment for type 2 diabetes mellitus, is well known to be subject to interindividual differences in bioavailability, leading to variations in therapeutic responses among patients. Distinct gut microbiota profiles among individuals are one of the most crucial yet commonly overlooked factors contributing to the variable bioavailability of numerous drugs. In light of the shift towards a more patient-centered approach in diabetes treatment, this study aimed to conduct a pharmacoinformatic analysis of gliclazide metabolites produced by gut microbiota and assess their docking potential with the SUR1 receptor to identify compounds with improved pharmacological profiles compared to the parent drug.
Ten potential gliclazide metabolites produced by the gut microbiota were screened for their pharmacological properties. Molecular docking analysis regarding SUR1 receptor was performed using Molegro Virtual Docker software. Drug-likeness properties were evaluated using DruLiTo software. Subsequently, the physicochemical and pharmacokinetic properties of gliclazide and its metabolites were determined by using VolSurf+ software package.
All studied metabolites exhibited better intrinsic solubility than gliclazide, which is of interest, considering that solubility is a limiting factor for its bioavailability. Based on the values of investigated molecular descriptors, hydroxylated metabolites M1-M6 showed the most pronounced polar and hydrophilic properties, which could significantly contribute to their