Effects of low-fat and high-fat meals on steady-state pharmacokinetics of lapatinib in patients with advanced solid tumours
| Autor: | Devriese, Lot A, Koch, Kevin M, Mergui-Roelvink, Marja, Matthys, Gemma M, Ma, Wen Wee, Robidoux, Andre, Stephenson, Joe J, Chu, Quincy S C, Orford, Keith W, Cartee, Leanne, Botbyl, Jeff, Arya, Nikita, Schellens, Jan H M, Sub Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male medicine.medical_specialty Receptor ErbB-2 Cmax Antineoplastic Agents Pharmacology Lapatinib Gastroenterology Food-Drug Interactions ErbB-2 Pharmacokinetics Neoplasms Internal medicine medicine Humans Pharmacology (medical) skin and connective tissue diseases Protein Kinase Inhibitors Aged Meal Cross-Over Studies business.industry digestive oral and skin physiology Middle Aged Dietary Fats Crossover study Oncology Tolerability Lapatinib ditosylate Toxicity Quinazolines business Receptor medicine.drug |
| Zdroj: | Investigational New Drugs, 32(3), 481. Kluwer Academic Publishers |
| ISSN: | 1573-0646 0167-6997 |
| DOI: | 10.1007/s10637-013-0055-4 |
| Popis: | AIM: To quantify the effect of food on the systemic exposure of lapatinib at steady state when administered 1 h before and after meals, and to observe the safety and tolerability of lapatinib under these conditions in patients with advanced solid tumours. METHODS: This was a three-treatment, randomised, three-sequence cross-over study. Lapatinib was administered 1 h after a low- [B] or a high-fat [C] meal and systemic exposure was compared with that obtained following administration 1 h before a low-fat meal [A]. RESULTS: In total, 25 patients were included, of whom 12 were evaluable for the pharmacokinetic analysis. Both low-fat and high-fat meals affected lapatinib exposure. Lapatinib AUC0-24 increased following lapatinib administration 1 h after a low-fat meal by 1.80-fold (90 % CI: 1.37-2.37) and after a high-fat meal by 2.61-fold (90 % CI: 1.98-3.43). Lapatinib Cmax increased following lapatinib administration 1 h after a low-fat meal by 1.90-fold (90 % CI: 1.49-2.43) and after a high-fat meal by 2.66-fold (90 % CI: 2.08-3.41). The most commonly occurring treatment-related toxicity was diarrhoea (8/25, 32 % CTCAE grade 1 and 2/25, 8 % grade 2) and one treatment-related grade ≥ 3 event occurred (fatigue grade 3, 4 %). CONCLUSIONS: Both low-fat and high-fat food consumed 1 h before lapatinib administration increased lapatinib systemic exposure compared with lapatinib administration 1 h before a low-fat meal. In order to administer lapatinib in a fasted state, it is advised to administer the drug 1 h before a meal. |
| Databáze: | OpenAIRE |
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