Influence of the Proton Pump Inhibitor Esomeprazole on the Bioavailability of Regorafenib: A Randomized Crossover Pharmacokinetic Study

Femke M. de Man*, Koen G.A.M. Hussaarts, Mirjam de With, Esther Oomen-de Hoop, Peter de Bruijn, Henk K. van Halteren, Nicole C.H.P. van der Burg-de Graauw, Ferry A.L.M. Eskens, Teun van Gelder, Roelof W.F. van Leeuwen, Ron H.J. Mathijssen

*Corresponding author for this work

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Abstract

Regorafenib exposure could potentially be influenced by an interaction with acid-reducing drugs. In this crossover trial, patients were randomized into two sequence groups consisting of three phases: regorafenib intake alone, regorafenib with concomitant esomeprazole, and regorafenib with esomeprazole 3 hours prior. The primary end point was the relative difference (RD) in geometric means for regorafenib 0–24-hour area under the concentration-time curve (AUC 0–24h ) and was analyzed by a linear mixed model in 14 patients. AUC 0–24h for regorafenib alone was 55.9 μg·hour/mL (coefficient of variance (CV): 40%), and for regorafenib with concomitant esomeprazole or with esomeprazole 3 hours prior AUC 0–24h was 53.7 μg·hour/mL (CV: 34%) and 53.6 μg·hour/mL (CV: 43%), respectively. No significant differences were identified when regorafenib alone was compared with regorafenib with concomitant esomeprazole (RD: −3.9%; 95% confidence interval (CI): −20.5 to 16.1%; P = 1.0) or regorafenib with esomeprazole 3 hours prior (RD: −4.1%; 95% CI: −22.8 to 19.2%; P = 1.0). These findings indicate that regorafenib and esomeprazole can be safely combined in clinical practice.

Original languageEnglish
Pages (from-to)1456-1461
Number of pages6
JournalClinical Pharmacology & Therapeutics
Volume105
Issue number6
DOIs
Publication statusPublished - Jun 2019

Bibliographical note

Funding Information:
This study was supported by an unrestricted grant from Bayer.

Funding Information:
This study was supported by an unrestricted grant from Bayer. This work has been presented at the 2018 ESMO Annual Meeting, #473 (Munich, Germany), October 2018.

Publisher Copyright:
© 2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics

Research programs

  • EMC MM-03-86-08

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