Agnieszka Karbownik1, Edyta Szałek2, Katarzyna Sobańska2, Agnieszka Klupczynska3, Szymon Plewa3, Tomasz Grabowski4, Anna Wolc5, Marta Moch2, Zenon J Kokot3, Edmund Grześkowiak2. 1. Department of Clinical Pharmacy and Biopharmacy, Poznań University of Medical Sciences, Poznań, Poland. Electronic address: agnieszkakarbownik@o2.pl. 2. Department of Clinical Pharmacy and Biopharmacy, Poznań University of Medical Sciences, Poznań, Poland. 3. Department of Inorganic and Analytical Chemistry, Poznań University of Medical Sciences, Poznań, Poland. 4. Polpharma Biologics, Gdańsk, Poland. 5. Department of Animal Science, Iowa State University, Ames, IA, USA; Hy-Line International, Dallas Center, IA USA.
Abstract
BACKGROUND: Diabetes mellitus (DM) is a complex metabolic disorder which affects the function of numerous tissues and alters the pharmacokinetic parameters of many drugs. As many oncological patients are diabetics, it is important to determine the influence of this chronic disease on the pharmacokinetics (PK) of anticancer drugs. Lapatinib is a tyrosine kinase inhibitor (TKI), approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The aim of the study was to compare the PK of lapatinib in normal and type 2 diabetes mellitus (T2DM) model rats. Additionally, the effect of lapatinib on blood glucose concentrations was examined. METHODS: The PK of lapatinib was studied in healthy rats (n=6, the healthy group) and T2DM model rats (n=6, the diabetic group). The rats received lapatinib orally as a single dose of 50mg. Plasma concentrations of lapatinib were measured with high-performance liquid chromatography method coupled with a tandem mass spectrometry. RESULTS: The plasma concentrations of lapatinib were increased in the T2DM model rats. There were statistically significant differences between the groups in Cmax (p=0.0104) and AUC0-t (p=0.0265). The reduction of glycaemia in the range of 1.2-41.5% and in the range of 4.1-36.8% was observed in the diabetic and healthy animals, respectively. CONCLUSIONS: Higher concentrations of lapatinib in the diabetic rats may suggest the need for application of lower doses of this TKI in patients with DM.
BACKGROUND:Diabetes mellitus (DM) is a complex metabolic disorder which affects the function of numerous tissues and alters the pharmacokinetic parameters of many drugs. As many oncological patients are diabetics, it is important to determine the influence of this chronic disease on the pharmacokinetics (PK) of anticancer drugs. Lapatinib is a tyrosine kinase inhibitor (TKI), approved for the treatment of humanepidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The aim of the study was to compare the PK of lapatinib in normal and type 2 diabetes mellitus (T2DM) model rats. Additionally, the effect of lapatinib on blood glucose concentrations was examined. METHODS: The PK of lapatinib was studied in healthy rats (n=6, the healthy group) and T2DM model rats (n=6, the diabetic group). The rats received lapatinib orally as a single dose of 50mg. Plasma concentrations of lapatinib were measured with high-performance liquid chromatography method coupled with a tandem mass spectrometry. RESULTS: The plasma concentrations of lapatinib were increased in the T2DM model rats. There were statistically significant differences between the groups in Cmax (p=0.0104) and AUC0-t (p=0.0265). The reduction of glycaemia in the range of 1.2-41.5% and in the range of 4.1-36.8% was observed in the diabetic and healthy animals, respectively. CONCLUSIONS: Higher concentrations of lapatinib in the diabeticrats may suggest the need for application of lower doses of this TKI in patients with DM.
Authors: Agnieszka Karbownik; Anna Stachowiak; Hanna Urjasz; Katarzyna Sobańska; Agnieszka Szczecińska; Tomasz Grabowski; Joanna Stanisławiak-Rudowicz; Anna Wolc; Edmund Grześkowiak; Edyta Szałek Journal: Pharmacol Rep Date: 2020-01-08 Impact factor: 3.024