Effect of the Proton Pump Inhibitor Esomeprazole on the Systemic Exposure of Capecitabine
| Autor: | Peter de Bruijn, Sander Bins, Ferry A.L.M. Eskens, Femke M. de Man, Ron H.J. Mathijssen, Niels Heersche, Esther Oomen-de Hoop, Leni van Doorn, Ivo Bijl, Ate van der Gaast |
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| Přispěvatelé: | Medical Oncology |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Male
Antimetabolites Antineoplastic medicine.medical_specialty medicine.drug_class Biological Availability Proton-pump inhibitor Carbonated Beverages Gastroenterology Esomeprazole Capecitabine Pharmacokinetics SDG 3 - Good Health and Well-being Neoplasms Internal medicine medicine Clinical endpoint Humans Drug Interactions Pharmacology (medical) Prospective Studies Netherlands Pharmacology Cross-Over Studies business.industry Proton Pump Inhibitors Middle Aged Drug interaction Crossover study Treatment Outcome Concomitant Female Drug Monitoring business medicine.drug |
| Zdroj: | Clinical Pharmacology and Therapeutics, 111(2), 455-460. Wiley-Blackwell |
| ISSN: | 1532-6535 0009-9236 |
| DOI: | 10.1002/cpt.2444 |
| Popis: | Retrospective data suggest that gastric acid reduction by proton pump inhibitors (PPIs) impairs the dissolution and subsequent absorption of capecitabine, and thus potentially reduces the capecitabine exposure. Therefore, we examined prospectively the effect of esomeprazole on the pharmacokinetics of capecitabine. In this randomized crossover study, patients with cancer were assigned to 2 sequence groups, each consisting of 3 phases: capecitabine with esomeprazole administration 3 hours before (phase A), capecitabine alone (phase B), and capecitabine concomitant with cola and esomeprazole co-administration 3 hours before (phase C). The primary end point was the relative difference (RD) in exposure to capecitabine assessed by the area under the plasma concentration-time curve from zero to infinity (AUC0-inf) and analyzed by a linear mixed effect model. Twenty-two evaluable patients were included in the analysis. After esomeprazole, there was a 18.9% increase in AUC0-inf of capecitabine (95% confidence interval (CI) −10.0% to 57.0%, P = 0.36). In addition, capecitabine half-life was significantly longer after esomeprazole (median 0.63 hours vs. 0.46 hours, P = 0.005). Concomitant cola did not completely reverse the effects observed after esomeprazole (RD 3.3% (95% CI −16.3 to 27.4%, P = 1.00). Capecitabine exposure is not negatively influenced by esomeprazole cotreatment. Therefore, altered capecitabine pharmacokinetics do not explain the assumed worse clinical outcome of PPI-cotreated patients with cancer. |
| Databáze: | OpenAIRE |
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