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 language | English (US) |
|---|---|
| Pages (from-to) | 481-488 |
| Number of pages | 8 |
| Journal | Investigational New Drugs |
| Volume | 32 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jan 1 2014 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
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.
PY - 2014/1/1
Y1 - 2014/1/1
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.
AB - 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.
KW - Food-effect
KW - Interaction
KW - Lapatinib ditosylate
KW - Oral chemotherapy
KW - Pharmacokinetics
KW - Tyrosine kinase inhibitor
UR - http://www.scopus.com/inward/record.url?scp=84904636722&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904636722&partnerID=8YFLogxK
U2 - 10.1007/s10637-013-0055-4
DO - 10.1007/s10637-013-0055-4
M3 - Article
C2 - 24346280
AN - SCOPUS:84904636722
VL - 32
SP - 481
EP - 488
JO - Investigational New Drugs
JF - Investigational New Drugs
SN - 0167-6997
IS - 3
ER -