title: Effects of low-fat and high-fat meals on steady-state pharmacokinetics of lapatinib in patients with advanced solid tumours.
abstract: OBJECTIVE
  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.affiliation: Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Lot A
authors.initials: LA
authors.lastname: Devriese
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Koch
authors.forename: Marja
authors.initials: M
authors.lastname: Mergui-Roelvink
authors.forename: Gemma M
authors.initials: GM
authors.lastname: Matthys
authors.forename: Wen Wee
authors.initials: WW
authors.lastname: Ma
authors.forename: Andre
authors.initials: A
authors.lastname: Robidoux
authors.forename: Joe J
authors.initials: JJ
authors.lastname: Stephenson
authors.forename: Quincy S C
authors.initials: QS
authors.lastname: Chu
authors.forename: Keith W
authors.initials: KW
authors.lastname: Orford
authors.forename: Leanne
authors.initials: L
authors.lastname: Cartee
authors.forename: Jeff
authors.initials: J
authors.lastname: Botbyl
authors.forename: Nikita
authors.initials: N
authors.lastname: Arya
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018565:Food-Drug Interactions; D006801:Humans; D000077341:Lapatinib; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004041:Dietary Fats; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human