Pharmacokinetic Evaluation of Antidiabetic FDCs - An In-Silico Approach
Abstract
Background: Drug Controller General of India (DCGI) approved the many (FDCs) fixed-dose combination where approximately more than 20 Antidiabetic fixed dose combination (FDCs) approved in every year. Objective: To evaluate the pharmacokinetic parameters of certain fixed-dose combinations using in silico computational tools. Methods: A total of 35 antidiabetic fixed-dose combinations were evaluated using SwissADME and vNN-ADMET computational tools. Pharmacokinetic and toxicity-related parameters, including gastrointestinal absorption, blood-brain permeability, P-glycoprotein substrate behavior, cytochrome P450 (CYP) enzyme interactions, drug-induced liver injury (DILI), and other ADMET characteristics, were analyzed comparatively. Pharmacokinetic mismatch was defined as the cumulative presence of multiple unfavorable ADMET parameters, rather than a single isolated predicted outcome. Results: 8 combinations with relatively unfavorable pharmacokinetic profiles and several ADMET-related liabilities—such as predicted DILI risk, CYP enzyme inhibition, poor absorption characteristics, and transporter-associated interactions like P-glycoprotein substrate behavior—were found by the in silico evaluation. For mismatch categorization, isolated positivity for P-gp substrates was deemed insufficient. With respectable drug-likeness and reduced anticipated toxicity, the remaining 27 combinations exhibited rather balanced pharmacokinetic profiles. Conclusion: An effective strategy for early…
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