Comparative in vitro assessment of CYP2C19 inhibition by ilaprazole and conventional proton pump inhibitors using a high throughput fluorometric assay
Abstract
Abstract Proton pump inhibitors (PPIs) are commonly used anti-ulcer agents, known to inhibit CYP2C19, leading to pharmacokinetic drug-drug interactions (DDIs). Ilaprazole is a newer PPI with a distinct pharmacokinetic profile that is predicted to overcome CYP2C19 inhibition. The current study aimed to predict the CYP2C19 inhibitory potential of Ilaprazole versus conventional PPIs (Omeprazole, Lansoprazole, Pantoprazole, and Rabeprazole) on CYP2C19 activity using a high-throughput fluorometric assay. The Vivid™ CYP2C19 Blue Screening Kit was utilized, and fluorescence intensity was measured after incubation with PPIs, using ticlopidine as a positive inhibitor control. The inhibition percentage was calculated, and IC50 values were determined using nonlinear regression analysis in graph pad prism, further, as per regulatory guidance, the C max,u /K i , u ratio was assessed to interpret the potential for clinical drug-drug interactions of PPIs. The concentration-dependent inhibition of CYP2C19 activity by all PPIs was evaluated. The order of inhibition potency, based on IC50 and K i , u values, was found to be: Omeprazole > Lansoprazole > Pantoprazole > Rabeprazole > Ilaprazole. The results of the C max,u /K i , u ratio indicate that Omeprazole (0.0288) exceeded the cut-off value consistent with its well-documented in vivo CYP2C19 inhibitory effect. While Lansoprazole (0.00332) had a relatively higher ratio than Ilaprazole (0.00224), Pantoprazole (0.00124), and Rabeprazole…
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