Pharmacokinetics and tissue distribution characteristics of sunitinib
10.12092/j.issn.1009-2501.2020.10.004
- VernacularTitle: 舒尼替尼药代动力学和脑肾组织分布特征
- Author:
Aiying CHEN
1
Author Information
1. Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, Institute of Medica Materia, Zhejing Academy of Medicine
- Publication Type:Journal Article
- Keywords:
Chromatographic condition;
HPLC-UV;
Pharmacokinetics;
Sunitinib;
Tissue distribution
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2020;25(10):1105-1110
- CountryChina
- Language:Chinese
-
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 (70:30) 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.
