Mechanistic competitive binding interaction study between olmutinib and colchicine with model transport protein using spectroscopic and computer simulation approaches

Drug-drug interactions are due to the binding of a drug to plasma proteins displacing another plasma protein-bound drug. Two ligands, olmutinib (OLM) and colchicine (COL), were explored for their binding and displacement interaction with bovine serum albumin (BSA). Olmutinib is a 3rd-generation tyrosine kinase in-hibitor (TKI), inhibits EGFR. COL is an anti-mitotic agent used in the treatment of gouty arthritis and has chemotherapeutic properties. The binding of BSA with OLM and COL was evaluated independently and in the presence of each other with spectroscopic and molecular docking and molecular dynamic simulation. Results based on quenching curves, displacement curves, binding constants, and docking results were evaluated. The presence of either drug (OLM or COL) influenced the binding of OLM and COL to BSA. The OLM had a higher binding capacity to BSA compared to COL. The presence of COL in the BSA-OLM system lowered the binding constants in comparison to its binary system. The OLM in the BSA-COL system increased the binding constant values for the system compared to the BSA-COL system. These findings are essential since increased non-bound fraction or reduced free drug fraction availability in the systemic circulation. The interference in the binding of drugs may lead to adverse events or subtherapeutic responses of the drugs.

Automated summary

This study investigated the binding and displacement interaction of olmutinib and colchicine with bovine serum albumin (BSA) using spectroscopic and molecular simulation methods. The presence of either drug influenced their binding to BSA, with olmutinib showing a higher binding capacity. These findings are important for understanding the pharmacological effects of these drugs in the body.