Pharmacokinetics and tissue distribution characteristics of sunitinib / 中国临床药理学与治疗学

ABSTRACT

AIM: To establish a HPLC-UV method to determine sunitinib in rat plasma and mouse tissues, and to study its pharmacokinetics in rats and tissue distribution characteristics in mice. METHODS: The biotic samples were prepared by protein precipitation followed by a stereoselective analysis of sunitinib was achieved on Waters XBridgeTM C18 (4.6 mm×250 mm, 5 μm) with a mobile phase composing of methanol-0.02 mol/L sodium dihydrogen phosphate (7030) at a flow rate of 1.0 mL/min. The detection wavelength was 310 nm, and the column temperature was 25 ℃. RESULTS: The calibration curve for rat plasma sunitinib was linear in the range of 0.019 2-15.34 μg/mL. The linear ranges in mice brain and kidney were 0.038 3-11.50 and 0.038 3-69.00 μg/mL, respectively. After intragastric administration of sunitinib at a dose of 20 mg/kg to rats, the pharmacokinetic characteristics were Tmax=9.0 h, Cmax=0.194 mg/L, t1/2=18.4 h, AUC(0-∞)=6.8 mg•L-1•h. And the absolute bioavailablity was 47.1%. It was indicated that sunitinib could permeate the blood brain barrier, but the concentration was lower in brain and higher in kidney. CONCLUSION: A HPLC-UV method for the determination of sunitinib in rat plasma and mouse tissues was established. The method is simple, rapid, reliable, and provides a reference for the clinical application of sunitinib.