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 journalArticle

25 Scopus citations

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 (US)
Pages (from-to)481-488
Number of pages8
JournalInvestigational New Drugs
Volume32
Issue number3
DOIs
StatePublished - Jun 2014

Keywords

  • Food-effect
  • Interaction
  • Lapatinib ditosylate
  • Oral chemotherapy
  • Pharmacokinetics
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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

    Devriese, L. A., Koch, K. M., Mergui-Roelvink, M., Matthys, G. M., Ma, W. W., Robidoux, A., Stephenson, J. J., Chu, Q. S. C., Orford, K. W., Cartee, L., Botbyl, J., Arya, N., & Schellens, J. H. M. (2014). Effects of low-fat and high-fat meals on steady-state pharmacokinetics of lapatinib in patients with advanced solid tumours. Investigational New Drugs, 32(3), 481-488. https://doi.org/10.1007/s10637-013-0055-4