title: Influence of the Acidic Beverage Cola on the Absorption of Erlotinib in Patients With Non-Small-Cell Lung Cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Roelof W F
authors: RW
authors: van Leeuwen
authors: 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.
authors: Robert
authors: R
authors: Peric
authors: 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.
authors: Koen G A M
authors: KG
authors: Hussaarts
authors: 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.
authors: Emma
authors: E
authors: Kienhuis
authors: 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.
authors: Nikki S
authors: NS
authors: IJzerman
authors: 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.
authors: Peter
authors: P
authors: de Bruijn
authors: 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.
authors: Cor
authors: C
authors: van der Leest
authors: 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.
authors: Henk
authors: H
authors: Codrington
authors: 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.
authors: Jeroen S
authors: JS
authors: Kloover
authors: 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.
authors: Bronno
authors: B
authors: van der Holt
authors: 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.
authors: Joachim G
authors: JG
authors: Aerts
authors: 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.
authors: Teun
authors: T
authors: van Gelder
authors: 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.
authors: Ron H J
authors: RH
authors: Mathijssen
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002253:Carbonated Beverages; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018592:Cross-Over Studies; D016903:Drug Monitoring; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D064098:Esomeprazole / Q000008:administration & dosage; D005260:Female; D018565:Food-Drug Interactions; D065569:Gastrointestinal Absorption; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D054328:Proton Pump Inhibitors / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D054328:Proton Pump Inhibitors; D000069347:Erlotinib Hydrochloride; D064098:Esomeprazole