Roelof W F van Leeuwen1, Robert Peric2, Koen G A M Hussaarts2, Emma Kienhuis2, Nikki S IJzerman2, Peter de Bruijn2, Cor van der Leest2, Henk Codrington2, Jeroen S Kloover2, Bronno van der Holt2, Joachim G Aerts2, Teun van Gelder2, Ron H J Mathijssen2. 1. Roelof W.F. van Leeuwen, Robert Peric, Koen G.A.M. Hussaarts, Emma Kienhuis, Nikki S. IJzerman, Peter de Bruijn, Cor van der Leest, Bronno van der Holt, Joachim G. Aerts, and Ron H.J. Mathijssen, Erasmus MC Cancer Institute; Roelof W.F. van Leeuwen and Teun van Gelder, Erasmus University Medical Center, Rotterdam; Cor van der Leest and Joachim G. Aerts, Amphia Hospital, Breda; Henk Codrington, Haga Hospital, the Hague; and Jeroen S. Kloover, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands. r.w.f.vanleeuwen@erasmusmc.nl. 2. Roelof W.F. van Leeuwen, Robert Peric, Koen G.A.M. Hussaarts, Emma Kienhuis, Nikki S. IJzerman, Peter de Bruijn, Cor van der Leest, Bronno van der Holt, Joachim G. Aerts, and Ron H.J. Mathijssen, Erasmus MC Cancer Institute; Roelof W.F. van Leeuwen and Teun van Gelder, Erasmus University Medical Center, Rotterdam; Cor van der Leest and Joachim G. Aerts, Amphia Hospital, Breda; Henk Codrington, Haga Hospital, the Hague; and Jeroen S. Kloover, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands.
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 [AUC0-12h]) 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 AUC0-12h increased 39% (range, -12% to 136%; P = .004), whereas in patients not treated with the PPI, the mean AUC0-12h 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.
RCT Entities:
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 [AUC0-12h]) 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 AUC0-12h increased 39% (range, -12% to 136%; P = .004), whereas in patients not treated with the PPI, the mean AUC0-12h 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.
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