Effects of low-fat and high-fat meals on steady-state pharmacokinetics of lapatinib in patients with advanced solid tumours

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

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)481-8
Number of pages8
JournalInvestigational New Drugs
Volume32
Issue number3
DOIs
Publication statusPublished - Jun 2014

Keywords

  • Adult
  • Aged
  • Antineoplastic Agents
  • Cross-Over Studies
  • Dietary Fats
  • Food-Drug Interactions
  • Humans
  • Male
  • Middle Aged
  • Neoplasms
  • Protein Kinase Inhibitors
  • Quinazolines
  • Receptor, ErbB-2

Fingerprint

Dive into the research topics of 'Effects of low-fat and high-fat meals on steady-state pharmacokinetics of lapatinib in patients with advanced solid tumours'. Together they form a unique fingerprint.

Cite this