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Influence of esomeprazole on the bioavailability of afatinib: A pharmacokinetic cross-over study in patients with non-small cell lung cancer.
Veerman, G D Marijn; Hurkmans, Daan P; Paats, Marthe S; Oomen-de Hoop, Esther; van der Leest, Cor H; van Thiel, Eric R E; Aerts, Joachim G J V; van Leeuwen, Roelof W; Dingemans, Anne-Marie C; Mathijssen, Ron H J.
Afiliación
  • Veerman GDM; Dept. of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. Electronic address: g.veerman@erasmusmc.nl.
  • Hurkmans DP; Dept. of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
  • Paats MS; Dept. of Pulmonology, Erasmus MC, Rotterdam, the Netherlands.
  • Oomen-de Hoop E; Dept. of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
  • van der Leest CH; Dept. of Pulmonology, Amphia Hospital, Breda, the Netherlands.
  • van Thiel ERE; Dept. of Pulmonology, Albert Schweitzer Hospital, Dordrecht, the Netherlands.
  • Aerts JGJV; Dept. of Pulmonology, Erasmus MC, Rotterdam, the Netherlands.
  • van Leeuwen RW; Dept. of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; Dept. of Hospital Pharmacy, Erasmus MC, Rotterdam, the Netherlands.
  • Dingemans AC; Dept. of Pulmonology, Erasmus MC, Rotterdam, the Netherlands.
  • Mathijssen RHJ; Dept. of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
Biomed Pharmacother ; 155: 113695, 2022 Nov.
Article en En | MEDLINE | ID: mdl-36126454
ABSTRACT
Afatinib is an oral small-molecule kinase inhibitor (SMKI) approved for treatment of metastatic non-small cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) driver mutation. Although oral administration is convenient, most SMKIs experience pH-dependent solubility. A drug-drug interaction between afatinib and proton-pump inhibitors (PPIs) has, however, never been studied in humans. Hence, we performed a randomized, three-period cross-over study. Afatinib (30 mg or 40 mg) was administered without PPI (period A), concomitantly with esomeprazole (period B) and three hours after esomeprazole intake (period C). Primary objective was the area under the curve (AUC0-24 h) comparing period A to period B and period A to period C. Secondary objectives were other pharmacokinetic parameters and toxicity. Linear mixed effect modelling was performed for differences in AUC0-24 h and Cmax between periods A and B and periods A and C. In 18 evaluable NSCLC patients, concomitant use of 40 mg esomeprazole decreased the steady-state afatinib AUC0-24 h with 10.2% (95% CI -29.2 to +14.0%; p = 0.564) compared to afatinib administration without PPI. Esomeprazole intake three hours prior to afatinib did not significantly influence afatinib AUC0-24 h (-0.6%; 95% CI -14.9 to +16.1%; p = 1.0). No differences in toxicity were observed. To conclude, esomeprazole did not change the exposure to afatinib in patients with NSCLC. Since there is no clinically relevant drug-drug interaction, esomeprazole can safely be co-administered with afatinib. This is important for clinical practice, because other EGFR-SMKIs (e.g. erlotinib and gefitinib) do experience clinically relevant drug-drug interactions with acid-suppressive agents.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Neoplasias Pulmonares Tipo de estudio: Clinical_trials / Prognostic_studies Idioma: En Revista: Biomed Pharmacother Año: 2022 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Neoplasias Pulmonares Tipo de estudio: Clinical_trials / Prognostic_studies Idioma: En Revista: Biomed Pharmacother Año: 2022 Tipo del documento: Article