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The pharmacokinetics and hypoglycaemic effect of sunitinib in the diabetic rabbits

Edyta Szałek1, Agnieszka Karbownik1, Katarzyna Sobańska1

  • 1Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznań, Poland.

Pharmacological Reports : PR
|August 24, 2014
PubMed
Abstract

Insights

Diabetes significantly alters sunitinib pharmacokinetics, increasing drug concentrations in diabetic rabbits. Sunitinib also demonstrated a notable hypoglycemic effect in both diabetic and normal rabbits.

Area of Science:

  • Pharmacology
  • Oncology
  • Endocrinology

Background:

  • Diabetes mellitus is a prevalent metabolic disease globally.
  • Sunitinib, a tyrosine kinase inhibitor (TKI), is used in cancer therapy and has a known hypoglycemic side effect.
  • Metabolic conditions like diabetes can alter drug pharmacokinetics and pharmacodynamics.

Purpose of the Study:

  • To compare sunitinib pharmacokinetics in diabetic versus non-diabetic rabbits.
  • To investigate the impact of diabetes on sunitinib concentrations after a single oral dose.
  • To evaluate the hypoglycemic effect of sunitinib in both diabetic and normoglycemic rabbits.

Main Methods:

  • A study involving two groups of rabbits: one diabetic (n=6) and one control (n=6).
  • Sunitinib was administered orally at a dose of 25mg.
  • Plasma concentrations of sunitinib and its metabolite SU12662 were quantified using validated High-Performance Liquid Chromatography (HPLC) with UV detection.

Main Results:

  • Diabetic rabbits showed significantly higher Cmax (1.63 times) and AUC0-∞ (2.03 times) for sunitinib compared to controls.
  • Statistically significant differences were observed in Cmax (p=0.006), AUC0-∞ (p=0.0088), and AUCkel (p=0.009).
  • A maximum blood glucose reduction of 14.4-69.6% was noted in diabetic rabbits and 15.4-33.5% in control rabbits, with levels returning to baseline within 24 hours.

Conclusions:

  • Diabetes significantly influences the pharmacokinetics of sunitinib.
  • The hypoglycemic effect of sunitinib was confirmed in both diabetic and normoglycemic rabbits.
  • These findings highlight potential therapeutic considerations for cancer patients with diabetes undergoing sunitinib treatment.
Keywords:
DiabetesHypoglycaemiaPharmacokineticsRabbitsSunitinib

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