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.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Devriese LA,Koch KM,Mergui-Roelvink M,Matthys GM,Ma WW,Robidoux A,Stephenson JJ,Chu QS,Orford KW,Cartee L,Botbyl J,Arya N,Schellens JHdoi
10.1007/s10637-013-0055-4subject
Has Abstractpub_date
2014-06-01 00:00:00pages
481-8issue
3eissn
0167-6997issn
1573-0646journal_volume
32pub_type
杂志文章,随机对照试验abstract::In this study, 30 evaluable patients with advanced carcinoma of the breast were treated with cyclophosphamide 600 mg/m2 i.v. followed one day later with mitoxantrone (Novantrone; dihydroxyanthracenedione) 16 mg/m2 i.v. Drug treatment was repeated every 3-4 weeks, for a maximum of 12 cycles. The overall response rate w...
journal_title:Investigational new drugs
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
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pub_type: 临床试验,杂志文章
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journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:Investigational new drugs
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pub_type: 临床试验,杂志文章,多中心研究
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journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章,多中心研究
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
pub_type: 杂志文章,评审
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journal_title:Investigational new drugs
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更新日期:1990-01-01 00:00:00