Campus Units
Animal Science
Document Type
Article
Publication Version
Published Version
Publication Date
2-20-2018
Journal or Book Title
Investigational New Drugs
Volume
36
First Page
819
Last Page
827
DOI
10.1007/s10637-018-0573-1
Abstract
Lapatinib is a tyrosine kinase inhibitor used for the treatment of breast cancer. Paracetamol is an analgesic commonly applied to patients with mild or moderate pain and fever. Cancer patients are polymedicated, which involves high risk of drug interactions during therapy. The aimof the study was to assess the interaction between lapatinib and paracetamol in rats. The rats were divided into three groups of eight animals in each. One group received lapatinib + paracetamol (IL+PA), another group received lapatinib (IIL), whereas the last group received paracetamol (IIIPA). A single dose of lapatinib (100 mg/kg b.w.) and paracetamol (100 mg/ kg b.w.) was administered orally. Plasma concentrations of lapatinib, paracetamol and its metabolites – glucuronide and sulphate, were measured with the validated HPLC-MS/MS method and HPLC-UV method, respectively. The pharmacokinetic parameters of both drugs were calculated using non-compartmental methods. The co-administration of lapatinib and paracetamol increased the area under the plasma concentration-time curve (AUC) and the maximum concentration (Cmax) of lapatinib by 239.6% (p = 0.0030) and 184% (p = 0.0011), respectively. Lapatinib decreased the paracetamol AUC0-∞ by 48.8% and Cmax by 55.7%. In the IL+PA group the Cmax of paracetamol glucuronide was reduced, whereas the Cmax of paracetamol sulphate was higher than in the IIIPA group. Paracetamol significantly affected the enhanced plasma exposure of lapatinib. Additionally, lapatinib reduced the concentrations of paracetamol. The co-administration of lapatinib decreased the paracetamol glucuronidation but increased the sulphation. The findings of this study may be of clinical relevance to patients requiring analgesic therapy.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Copyright Owner
The Authors
Copyright Date
2018
Language
en
File Format
application/pdf
Recommended Citation
Karbownik, Agnieszka; Szałek, Edyta; Sobańska, Katarzyna; Grabowski, Tomasz; Klupczynska, Agnieszka; Plewa, Szymon; Wolc, Anna; Magiera, Magdalena; Porażka, Joanna; Kokot, Zenon J.; and Grześkowiak, Edmund, "The concomitant use of lapatinib and paracetamol - the risk of interaction" (2018). Animal Science Publications. 622.
https://lib.dr.iastate.edu/ans_pubs/622
Included in
Agriculture Commons, Animal Experimentation and Research Commons, Animal Sciences Commons, Pharmacy and Pharmaceutical Sciences Commons
Comments
This article is published as Karbownik, A., Szałek, E., Sobańska, K. et al. The concomitant use of lapatinib and paracetamol - the risk of interaction. Invest New Drugs 36, 819–827 (2018). doi: 10.1007/s10637-018-0573-1.