Assessment of Pharmacokinetic Interaction and Clinical Efficacy of Clopidogrel Co‐administered with Ilaprazole

Abstract

Clopidogrel is often co‐prescribed with proton pump inhibitors (PPIs) to reduce gastrointestinal bleeding risk. However, some PPIs, especially pantoprazole, inhibit CYP2C19, potentially reducing clopidogrel's activation. Ilaprazole, a newer PPI primarily metabolized via CYP3A4, may offer reduced interaction. The study was an open‐label, randomized trial that involved 36 healthy male volunteers, who were divided into three groups (n = 12 each): Group 1 (Clopidogrel + Placebo), Group 2 (Clopidogrel + Pantoprazole 40 mg), and Group 3 (Clopidogrel + Ilaprazole 10 mg). After 7 days of treatment, all participants received clopidogrel 75 mg on Day 8. Pharmacokinetic (PK) parameters were analyzed using LC‐MS/MS and platelet aggregation by light transmission aggregometry at 0, 4, 10, and 24 h. Pantoprazole significantly reduced clopidogrel AUC (1.96 ± 0.20 vs 8.27 ± 1.04 ng·h/mL, P < .0005), C _max (0.76 ± 0.04 vs 2.6 ± 1.01 ng/mL, P = .0136), and t ₁ / ₂ (1.72 ± 0.11 vs 2.22 ± 0.17 h, P = .0312), indicating reduced bioavailability. Geometric mean ratio (GMR) analysis showed a marked reduction in clopidogrel exposure with pantoprazole (C _max GMR 0.31, 90% CI 0.18–0.53; AUC GMR 0.24, 90% CI 0.19–0.29), and platelet aggregation was significantly higher at 4 and 10 h ( P < .05). In contrast, ilaprazole preserved PK parameters (AUC 10.18 ± 1.41, C _max 3.06 ± 1.05), GMRs near unity (C _max 1.20, 90% CI 0.60–2.42; AUC 1.23, 90% CI 0.97–1.55), indicating no inhibitory effect and platelet inhibition comparable to placebo ( P > .05) Ilaprazole did not affect clopidogrel pharmacokinetics or pharmacodynamics, suggesting it as a safer alternative to pantoprazole in dual antiplatelet therapy.