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 max (0.76 ± 0.04 vs 2.6 ± 1.01 ng/mL, P = .0136), and t1/2 (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 (Cmax 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 max 3.06 ± 1.05), GMRs near unity (Cmax 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…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 36 participants or records.
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