| Autor: |
G.D. Marijn Veerman, Daan P. Hurkmans, Marthe S. Paats, Esther Oomen-de Hoop, Cor H. van der Leest, Eric R.E. van Thiel, Joachim G.J.V. Aerts, Roelof W. van Leeuwen, Anne-Marie C. Dingemans, Ron H.J. Mathijssen |
| Přispěvatelé: |
Medical Oncology, Pathology, Pulmonary Medicine, Hematology, Pharmacy |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Biomedicine and Pharmacotherapy, 155:113695. Elsevier Masson |
| ISSN: |
0753-3322 |
| DOI: |
10.1016/j.biopha.2022.113695 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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