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.
RCT Entities:
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.
Authors: M Maliepaard; G L Scheffer; I F Faneyte; M A van Gastelen; A C Pijnenborg; A H Schinkel; M J van De Vijver; R J Scheper; J H Schellens Journal: Cancer Res Date: 2001-04-15 Impact factor: 12.701
Authors: D J Slamon; W Godolphin; L A Jones; J A Holt; S G Wong; D E Keith; W J Levin; S G Stuart; J Udove; A Ullrich Journal: Science Date: 1989-05-12 Impact factor: 47.728
Authors: John P Crown; Harold A Burris; Fran Boyle; Suzanne Jones; Maria Koehler; Beth O Newstat; Roma Parikh; Cristina Oliva; Alaknanda Preston; Julie Byrne; Steve Chan Journal: Breast Cancer Res Treat Date: 2008-01-20 Impact factor: 4.872
Authors: Kevin M Koch; Nandi J Reddy; Roger B Cohen; Nancy L Lewis; Bonnie Whitehead; Kathleen Mackay; Andrew Stead; Andrew P Beelen; Lionel D Lewis Journal: J Clin Oncol Date: 2009-02-02 Impact factor: 44.544
Authors: Stephen Johnston; John Pippen; Xavier Pivot; Mikhail Lichinitser; Saeed Sadeghi; Veronique Dieras; Henry Leonidas Gomez; Gilles Romieu; Alexey Manikhas; M John Kennedy; Michael F Press; Julie Maltzman; Allison Florance; Lisa O'Rourke; Cristina Oliva; Steven Stein; Mark Pegram Journal: J Clin Oncol Date: 2009-09-28 Impact factor: 44.544
Authors: Huixin Yu; Neeltje Steeghs; Cynthia M Nijenhuis; Jan H M Schellens; Jos H Beijnen; Alwin D R Huitema Journal: Clin Pharmacokinet Date: 2014-04 Impact factor: 6.447
Authors: Kari B Wisinski; Amye J Tevaarwerk; Mark E Burkard; Murtuza Rampurwala; Jens Eickhoff; Maria C Bell; Jill M Kolesar; Christopher Flynn; Glenn Liu Journal: Clin Cancer Res Date: 2016-03-29 Impact factor: 12.531
Authors: B Milojkovic Kerklaan; S Slater; M Flynn; A Greystoke; P O Witteveen; M Megui-Roelvink; F de Vos; E Dean; L Reyderman; L Ottesen; M Ranson; M P J Lolkema; R Plummer; R Kristeleit; T R J Evans; J H M Schellens Journal: Invest New Drugs Date: 2016-04-02 Impact factor: 3.850
Authors: Russell Z Szmulewitz; Cody J Peer; Abiola Ibraheem; Elia Martinez; Mark F Kozloff; Bradley Carthon; R Donald Harvey; Paul Fishkin; Wei Peng Yong; Edmund Chiong; Chadi Nabhan; Theodore Karrison; William D Figg; Walter M Stadler; Mark J Ratain Journal: J Clin Oncol Date: 2018-03-28 Impact factor: 50.717
Authors: Hany W Darwish; Ahmed H Bakheit; Nasser S Al-Shakliah; A F M Motiur Rahman; Ibrahim A Darwish Journal: PLoS One Date: 2020-12-03 Impact factor: 3.240