Interaction of propoxazepam with human liver cytochrome P450 2C9 and its therapeutic implications

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Propoxazepam is a novel benzodiazepine-derived analgesic that has completed Phase I clinical trials, demonstrating its safety and appropriate pharmacokinetics. Phase II trials are currently underway. We investigated the interaction of propoxazepam with cytochrome P450 2C9, one of the key human liver isoenzymes responsible for metabolizing many drugs. Using spectrophotometric titration and molecular docking methods, we found that propoxazepam exhibits a low-affinity binding to CYP2C9, suggesting a minimal risk of competitive inhibition of this enzyme. The docking analysis also revealed a potential binding pose of propoxazepam in the enzyme’s active site, consistent with the observed spectroscopic data. These findings indicate a low probability of pharmacokinetic interactions between propoxazepam and other CYP2C9 substrates, supporting its further development as a safe analgesic. The results have important implications for the clinical use of propoxazepam in patients taking other medications metabolized by CYP2C9.