Influence of the Acidic Beverage Cola on the Absorption of Erlotinib in Patients With Non-Small-Cell Lung Cancer

Roelof van Leeuwen, Robert Peric, Koen Hussaarts, Emma Kienhuis, Nikki IJzerman, Peter de Bruijn, Kornelis Leest, H Codrington, JS Kloover, Ronnie van der Holt, Joachim Aerts, Teun Gelder, Ron Mathijssen

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Abstract

Purpose Erlotinib depends on stomach pH for its bioavailability. When erlotinib is taken concurrently with a proton pump inhibitor (PPI), stomach pH increases, which results in a clinically relevant decrease of erlotinib bioavailability. We hypothesized that this drug-drug interaction is reversed by taking erlotinib with the acidic beverage cola. The effects of cola on erlotinib bioavailability in patients not treated with a PPI were also studied. Patients and Methods In this randomized, cross-over, pharmacokinetic study in patients with non-small-cell lung cancer, we studied intrapatient differences in absorption (area under the plasma concentration time curve [AUC(0-12h)]) after a 7-day period of concomitant treatment with erlotinib, with or without esomeprazole, with either cola or water. At the 7th and 14th day, patients were hospitalized for 1 day for pharmacokinetic sampling. Results Twenty-eight evaluable patients were included in the analysis. In patients treated with erlotinib and esomeprazole with cola, the mean AUC(0-12h) increased 39% (range, -12% to 136%; P = .004), whereas in patients not treated with the PPI, the mean AUC(0-12h) was only slightly higher (9%; range, -10% to +30%; P = .03) after erlotinib intake with cola. Conclusion Cola intake led to a clinically relevant and statistically significant increase in the bioavailability of erlotinib during esomeprazole treatment. In patients not treated with the PPI, the effects of cola were marginal. These findings can be used to optimize the management of drug-drug interactions between PPIs and erlotinib. (C) 2016 by American Society of Clinical Oncology
Original languageUndefined/Unknown
Pages (from-to)1309-1314
Number of pages6
JournalJournal of Clinical Oncology
Volume34
Issue number12
DOIs
Publication statusPublished - 2016

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