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.
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