Lack of a Clinically Significant Drug-drug Interaction in Healthy Volunteers Between the HCV Protease Inhibitor Boceprevir and the Proton Pump Inhibitor Omeprazole
de Kanter CT, Colbers AP, Blonk MI, Verweij-van Wissen CP, Schouwenberg BJ, Drenth JP, Burger DM
OBJECTIVES: Proton pump inhibitors (PPIs) can limit the solubility of concomitant drugs, which can lead to decreased absorption and exposure. Reduced efficacy can be a consequence and in the case of an antimicrobial agent this may contribute to development of resistance. Patients chronically infected with the hepatitis C virus can be treated with a boceprevir-containing regimen and it is relevant to know if interactions between PPIs and boceprevir exist. This study was designed to investigate the influence of a frequently used PPI, omeprazole, on the pharmacokinetics of boceprevir and vice versa.
METHODS: In this open-label, three-period, randomized, cross-over, Phase I study, healthy subjects were randomly assigned to 40 mg of omeprazole once daily for 5 days, 800 mg of boceprevir three times daily for 5 days and 40 mg of omeprazole once daily?00 mg of boceprevir three times daily for 5 days, or the same treatment in a different order. Every treatment was followed by a wash-out period. At day 5 of every treatment pharmacokinetic blood sampling was performed for 8 h after medication intake. ClinicalTrials.gov: NCT01470690.
RESULTS: All 24 subjects (15 males) completed the study and no serious adverse events were reported. Geometric mean ratios (90% CI) of the area under the plasma concentration-time curve up to 8 h (AUC(0-8)) and maximum plasma concentration (C(max)) of boceprevir with omeprazole versus boceprevir alone were 0.92 (0.87-0.97) and 0.94 (0.86-1.02), respectively. For omeprazole these values were 1.06 (0.90-1.25) for AUC(0-8) and 1.03 (0.85-1.26) for C(max) for the combination versus omeprazole alone.
CONCLUSIONS: Omeprazole did not have a clinically significant effect on boceprevir exposure, and boceprevir did not affect omeprazole exposure.
