title: The pharmacokinetics and hypoglycaemic effect of sunitinib in the diabetic rabbits.
abstract: BACKGROUND
  Diabetes is one of the most common metabolic diseases in the world, which may influence changes in the pharmacokinetics and pharmacodynamics of drugs. Sunitinib is a tyrosine kinase inhibitor (TKI) broadly used for treatment of numerous cancers, which exhibits the side hypoglycaemic effect. The aim of the study was a comparison of concentrations and pharmacokinetics of sunitinib after a single administration in rabbits with hyperglycaemia and normoglycaemia (control group). Additionally, the effect of sunitinib on glucose levels was investigated.
  
  
  METHODS
  The research was carried out on a control group (n=6) and a group of rabbits with diabetes (n=6). The rabbits were treated with sunitinib in the oral dose of 25mg. Plasma concentrations of sunitinib and its metabolite (SU12662) were measured with validated HPLC method with UV detection.
  
  
  RESULTS
  The comparison of the sunitinib Cmax and AUC0-∞ in the diabetic group with the control group gave the ratios of 1.63 [90% confidence interval (CI) [1.59; 1.66] and 2.03 [1.97; 2.09], respectively. Statistically significant differences between the analyzed groups were revealed for Cmax (p=0.006), AUC0-∞ (p=0.0088), and AUCkel (p=0.009). The maximum glycaemia drop of 14.4-69.6% and 15.4-33.5% was observed in the diabetic animals and in the control group, respectively. The glycaemia values returned to the initial values in 24h after the administration of the drug.
  
  
  CONCLUSIONS
  The research proved the significant influence of diabetes on the pharmacokinetics of sunitinib and it confirmed the hypoglycaemic effect of the TKI in diabetic rabbits and in normoglycaemia.
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland. Electronic address: szalekedyta@wp.pl.
authors.forename: Edyta
authors.initials: E
authors.lastname: Szałek
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: 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 Urology, University Clinical Centre, Gdańsk, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Połom
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Lewandowska
authors.affiliation: Department of Animal Science, Iowa State University, IA, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Wolc
authors.affiliation: Department of Urology, University Clinical Centre, Gdańsk, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Matuszewski
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: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D007211:Indoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D011758:Pyrroles / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D000077210:Sunitinib
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; C544393:SU 12662; D000077210:Sunitinib
keywords: Diabetes; Hypoglycaemia; Pharmacokinetics; Rabbits; Sunitinib