The penetration of sunitinib through the blood-brain barrier after the administration of ciprofloxacin.

Sunitinib (SU 11248) is an efficacious antineoplastic and antiangiogenic drug from the group of tyrosine kinase inhibitors (TKIs). In 2006, SUTENT (Pfizer) was registered by the US Food and Drug Administration (FDA) for the treatment of gastrointestinal stromal tumor (GIST) if the imatinib therapy is unsuccessful and for the treatment of renal cell carcinoma (RCC) (1). In 2011, SUTENT was recommended by the FDA for the treatment of progressive pancreatic neuroendocrine tumors (2). Apart from the indications listed above, the drug may also be efficacious in non-small-cell lung cancer, breast cancer and neuroendocrine neoplasms (3). The drug achieves its antineoplastic effect by inhibition of the following receptors: plateletderived growth factor receptors (PDGFRa and PDGFRb), vascular endothelial growth factor receptors (VEGFR1, VEGFR2, VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase receptor-3 (FLT3), colony stimulating factor receptor (CSF-1R), glial cell line-derived neurotrophic factor receptor (RET). The pharmacokinetics of sunitinib was studied in a number of investigations. The bioavailability of the drug in animals is about 50% (4). The maximum concentration of the drug in the plasma (Cmax) is observed between 6 and 12 h after the administration (5). A daily dose of 50 mg of sunitinib gives a possibility to reach the steady-state concentration of 50ñ100 ng/mL, which influences the pharmacological effect of the drug (6). The time necessary to achieve the steady state is 7ñ14 days for sunitinib and about 14 days for its active metabolite SU 12662 (N-desethylsunitinib). The administration of the drug once a day for 14 days causes the concentration of sunitinib to increase 4.5 times; the concentration of the active metabolite increases 10 times and the complete fraction of the drug (sunitinib plus SU 12662) increases 5 times (7). CYP3A4 has been proved to be involved in the metabolism of sunitinib and its major circulating metabolite (SU 12662) (5, 6, 8), which unfortunately may be the cause of interaction with the inhibitors or inductors of this enzyme when they are simultaneously applied (9). At present, there are only a few publications available, which support the opinion that sunitinib may cross the blood-brain barrier. However, few authors confirm sunitinib activity in brain metastases from kidney cancer (10ñ13). Patyna et al. (14) showed rapid distribution of [C]-sunitinib and its metabolite in the brain and spinal cord tissue after intravenous or oral administration of the drug to monkeys, rats and mice. The conclusion of the research was the need to continue it due to the antitumor activity in the brain. There is growing interest in the subject because of the efficaciousness of suniSHORT COMMUNICATION