title: The alteration of pharmacokinetics of erlotinib and OSI420 in type 1 diabetic rabbits.
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.
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Karbownik
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Szałek
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland. Electronic address: sobanska.katarzyna@gmail.com.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Sobańska
authors.affiliation: Polpharma Biologics, Gdańsk, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Grabowski
authors.affiliation: Department of Animal Science, Iowa State University, Ames, USA; Hy-Line International, Dallas Center, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Wolc
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Edmund
authors.initials: E
authors.lastname: Grześkowiak
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D001786:Blood Glucose / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D000069347:Erlotinib Hydrochloride / Q000493:pharmacokinetics*; D005260:Female; D008297:Male; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics*; D011817:Rabbits; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D001786:Blood Glucose; D047428:Protein Kinase Inhibitors; D003841:Deoxycytidine; D000069347:Erlotinib Hydrochloride; D000093542:Gemcitabine
keywords: Diabetes; Erlotinib; OSI420; Pharmacokinetics; Rabbit