Erschienen in:
01.06.2014 | PHASE I STUDIES
Effects of low-fat and high-fat meals on steady-state pharmacokinetics of lapatinib in patients with advanced solid tumours
verfasst von:
Lot A. Devriese, Kevin M. Koch, Marja Mergui-Roelvink, Gemma M. Matthys, Wen Wee Ma, Andre Robidoux, Joe J. Stephenson, Quincy S. C. Chu, Keith W. Orford, Leanne Cartee, Jeff Botbyl, Nikita Arya, Jan H. M. Schellens
Erschienen in:
Investigational New Drugs
|
Ausgabe 3/2014
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Summary
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.