Campus Units
Animal Science
Document Type
Article
Publication Version
Published Version
Publication Date
2019
Journal or Book Title
Acta Poloniae Pharmaceutica – Drug Research
Volume
76
Issue
4
First Page
645
Last Page
651
Abstract
Lapatinib is a tyrosine kinase inhibitor used to treat patients with locally advanced or metastatic breast cancer exhibiting overexpression of the human epidermal growth factor receptor 2 (HER2 receptor, ErbB2). Preclinical and clinical studies suggest that lapatinib is mainly metabolized by CYP3A4, therefore the study in an animal model was designed to investigate the pharmacokinetic interaction of lapatinib and clarithromycin, a well-known CYP3A4 inhibitor. The rats were subjected to one of the two study groups: lapatinib + clarithromycin (ILap+Clar; n = 6), and lapatinib + placebo (IILap; n = 6). The animals were treated with lapatinib in the oral single dose of 100 mg/kg. The antibiotic was administered orally at a dose of 25 mg/kg. Blood sampling was performed until 30 hours after dosing for pharmacokinetic assays. Plasma concentrations of lapatinib were measured by liquid chromatography-mass spectrometry. The comparison of lapatinib maximum concentration and area under the concentration-time curve in the ILap+Clar with the control group IILap gave the ratios of 1.38 (90% confidence interval (CI)) (1.14; 1.68) and 1.16 (0.75; 1.79), respectively. A statistically significant difference between analyzed groups was revealed only for maximum concentration (p = 0.0107). Single oral administration of clarithromycin significantly increased the concentration of lapatinib in rats, therefore caution should be taken during concomitant treatment with this macrolide and the tyrosine kinase inhibitor in patients.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Copyright Owner
Polish Pharmaceutical Society
Copyright Date
2019
Language
en
File Format
application/pdf
Recommended Citation
Karbownik, Agnieszka; Porazka, Joanna; Luczak, Anna; Tezyk, Artur; Grabowski, Tomasz; Wolc, Anna; Grzeskowiak, Edmund; and Szalek, Edyta, "Pharmacokinetic interaction after oral coadministration of clarithromycin and the tyrosine kinase inhibitor lapatinib in rats" (2019). Animal Science Publications. 658.
https://lib.dr.iastate.edu/ans_pubs/658
Included in
Animal Experimentation and Research Commons, Animal Sciences Commons, Medicinal Chemistry and Pharmaceutics Commons
Comments
This article is published as Karbownik A., Porazka J, Luczak A., Tezyk A., Grabowski T., Wolc A., Grzeskowiak E., Szalek E. 2019. Pharmacokinetic interaction after oral coadministration of clarithromycin and the tyrosine kinase inhibitor lapatinib in rats. Acta Poloniae Pharmaceutica – Drug Research 76(4): 645-651.