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

22 Citations (Scopus)

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 - Jan 1 2014
Externally publishedYes

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Meals
Pharmacokinetics
Fats
Neoplasms
lapatinib
Food
Cross-Over Studies
Fatigue
Diarrhea
Therapeutics
Safety

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Cite this

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

In: Investigational New Drugs, Vol. 32, No. 3, 01.01.2014, p. 481-488.

Research output: Contribution to journalArticle

Devriese, LA, Koch, KM, Mergui-Roelvink, M, Matthys, GM, Ma, WW, Robidoux, A, Stephenson, JJ, Chu, QSC, Orford, KW, Cartee, L, Botbyl, J, Arya, N & Schellens, JHM 2014, 'Effects of low-fat and high-fat meals on steady-state pharmacokinetics of lapatinib in patients with advanced solid tumours', Investigational New Drugs, vol. 32, no. 3, pp. 481-488. https://doi.org/10.1007/s10637-013-0055-4
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. / Effects of low-fat and high-fat meals on steady-state pharmacokinetics of lapatinib in patients with advanced solid tumours. In: Investigational New Drugs. 2014 ; Vol. 32, No. 3. pp. 481-488.
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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.",
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T1 - Effects of low-fat and high-fat meals on steady-state pharmacokinetics of lapatinib in patients with advanced solid tumours

AU - Devriese, Lot A.

AU - Koch, Kevin M.

AU - Mergui-Roelvink, Marja

AU - Matthys, Gemma M.

AU - Ma, Wen Wee

AU - Robidoux, Andre

AU - Stephenson, Joe J.

AU - Chu, Quincy S.C.

AU - Orford, Keith W.

AU - Cartee, Leanne

AU - Botbyl, Jeff

AU - Arya, Nikita

AU - Schellens, Jan H.M.

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N2 - 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.

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KW - Pharmacokinetics

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