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

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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.

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Acknowledgments

This study was funded by GlaxoSmithKline group of companies. Editorial support was provided by James Andrews and Karen Yee at FWG Scientific Communications and funded by GlaxoSmithKline.

Conflict of interest

All authors have completed the unified Competing Interest Form at http://www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: LAD, JHMS, MMR, QC, WWM, and JS have no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years. AR received institute support for the submitted study from GlaxoSmithKline and has consulted for Novartis. JB is an employee of Provonix LLC, contracted to GSK for statistical services. GM, KK, KWO, LC and NA are employees of GSK and hold stock options.

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Authors and Affiliations

  1. Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Lot A. Devriese & Jan H. M. Schellens

  2. Department of Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Lot A. Devriese, Marja Mergui-Roelvink & Jan H. M. Schellens

  3. Medicines Discovery and Development, Research & Development, GlaxoSmithKline, Philadelphia, PA, USA

    Kevin M. Koch & Nikita Arya

  4. Oncology Global Business, Research & Development, GlaxoSmithKline, Philadelphia, PA, USA

    Gemma M. Matthys, Keith W. Orford & Leanne Cartee

  5. Roswell Park Cancer Institute, Buffalo, NY, USA

    Wen Wee Ma

  6. Centre Hospitalier de l’Université de Montréal-Hotel-Dieu de Montréal, Quebec, Canada

    Andre Robidoux

  7. Greenville Hospital System Institute for Translational Oncology Research, Greenville, SC, USA

    Joe J. Stephenson

  8. Cross Cancer Institute, Edmonton, AB, Canada

    Quincy S. C. Chu

  9. Provonix, contractor to GlaxoSmithKline, Philadelphia, PA, USA

    Jeff Botbyl

  10. Science Faculty, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

    Jan H. M. Schellens

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  1. Lot A. Devriese
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Correspondence to Jan H. M. Schellens.

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Devriese, L.A., Koch, K.M., Mergui-Roelvink, M. et al. Effects of low-fat and high-fat meals on steady-state pharmacokinetics of lapatinib in patients with advanced solid tumours. Invest New Drugs 32, 481–488 (2014). https://doi.org/10.1007/s10637-013-0055-4

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  • DOI: https://doi.org/10.1007/s10637-013-0055-4

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