Exploring Ilaprazole-CYP2C19 interaction: A computational study on metabolic stability and drug-drug interaction potential

Proton pump inhibitors (PPIs) have been shown to reduce the therapeutic efficacy and alter the clinical outcomes of co-administered medications due to cytochrome P450 family 2 subfamily C member 19 (CYP2C19) enzyme inhibition . Compared with conventional PPIs, Ilaprazole may have a minimal or negligible inhibitory effects on CYP2C19, potentially lowering the risk of drug-drug interactions, as per the results of preliminary studies and its pharmacokinetic variability. This study aimed to evaluate the CYP2C19 interaction potential of ilaprazole versus conventional PPIs using a computational approach (SuperCYP and SMARTCyp). This was a computational in silico study combining database-driven predictions (SuperCYP) with structure-based metabolism modeling (SMARTCyp). Computational techniques such as SuperCYP predict cytochrome P450 (CYP450) interactions (inhibition, induction, or substrate affinity) of drugs and SMARTCyp predicts sites of metabolism (SOM) in small molecules by CYP450 enzymes, specifically identifying vulnerable atoms within drug structure. Based on MORGAN and MACCS fingerprints, ilaprazole was predicted to be inactive for CYP2C19 inhibition, with a low probability value (0.552–0.587) using cytochrome enzyme inhibition activity. SMARTCyp predicts SOM by the cytochrome P450 family 3 subfamily A member 4 (CYP3A4) enzyme, where a lower 3A4 ranking and score (S.9 with 41.5) indicate a higher probability of metabolism, and lower energy values (S.9 with 46.9) suggest increased reactivity. Higher 2DSASA values (C.26 with 64.3) indicated stronger enzyme-substrate interactions. This study supports the hypothesis that ilaprazole does not inhibit CYP2C19, as evidenced by its low probability and inactivity predictions.