Agnieszka Karbownik1, Edyta Szałek1, Katarzyna Sobańska2, Tomasz Grabowski3, Anna Wolc4, Edmund Grześkowiak1. 1. Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland. 2. Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland. Electronic address: sobanska.katarzyna@gmail.com. 3. Polpharma Biologics, Gdańsk, Poland. 4. Department of Animal Science, Iowa State University, Ames, USA; Hy-Line International, Dallas Center, USA.
Abstract
BACKGROUND: Alterations in blood glucose levels observed in diabetes, may change the pharmacokinetics of co-administered drugs and in consequence, the efficacy and safety of therapy. Many oncological patients are diabetics and it is important to determine the interaction of anticancer drugs with this chronic disease. Erlotinib is a tyrosine kinase inhibitor (TKI), approved for the treatment of patients with non-small-cell lung cancer and pancreatic cancer in combination with gemcitabine. The aim of the study was to investigate the influence of the diabetes on the pharmacokinetics of erlotinib in rabbits. Additionally, the effect of erlotinib on glucose levels was examined. METHODS: The pharmacokinetics of erlotinib was studied in healthy rabbits (n=6, control group) and type 1 diabetic rabbits (n=6, diabetic group). Erlotinib was administered in a single oral dose of 25mg. Plasma concentrations of erlotinib and its metabolite (OSI420) were measured with the validated method. RESULTS: The plasma concentrations of erlotinib and OSI420 were markedly increased in diabetic rabbits. Statistically significant differences between the groups were revealed for almost all analysed pharmacokinetic parameters for erlotinib and OSI420. The maximum glycaemia drop of 7.7-33.5% was observed in the diabetic animals, but no significant changes in glucose concentration were observed in the control group. CONCLUSIONS: The research proved the significant influence of diabetes on the pharmacokinetics of erlotinib and OSI420. Due to higher exposure to erlotinib, there may be an increased risk of adverse drug reactions in diabetic patients. Therefore, in some cases lower doses of the drug should be considered.
BACKGROUND: Alterations in blood glucose levels observed in diabetes, may change the pharmacokinetics of co-administered drugs and in consequence, the efficacy and safety of therapy. Many oncological patients are diabetics and it is important to determine the interaction of anticancer drugs with this chronic disease. Erlotinib is a tyrosine kinase inhibitor (TKI), approved for the treatment of patients with non-small-cell lung cancer and pancreatic cancer in combination with gemcitabine. The aim of the study was to investigate the influence of the diabetes on the pharmacokinetics of erlotinib in rabbits. Additionally, the effect of erlotinib on glucose levels was examined. METHODS: The pharmacokinetics of erlotinib was studied in healthy rabbits (n=6, control group) and type 1 diabetic rabbits (n=6, diabetic group). Erlotinib was administered in a single oral dose of 25mg. Plasma concentrations of erlotinib and its metabolite (OSI420) were measured with the validated method. RESULTS: The plasma concentrations of erlotinib and OSI420 were markedly increased in diabetic rabbits. Statistically significant differences between the groups were revealed for almost all analysed pharmacokinetic parameters for erlotinib and OSI420. The maximum glycaemia drop of 7.7-33.5% was observed in the diabetic animals, but no significant changes in glucose concentration were observed in the control group. CONCLUSIONS: The research proved the significant influence of diabetes on the pharmacokinetics of erlotinib and OSI420. Due to higher exposure to erlotinib, there may be an increased risk of adverse drug reactions in diabeticpatients. Therefore, in some cases lower doses of the drug should be considered.
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