Targeted distribution study of 5-fluorouracil-D-glucosamine derivative in mice
10.13699/j.cnki.1001-6821.2017.22.018
- VernacularTitle:D-氨基葡萄糖修饰的5-氟尿嘧啶衍生物在动物体内靶向性研究
- Author:
Dan ZHENG
1
;
Qin YANG
Author Information
1. 四川大学华西药学院
- Keywords:
5-fluorouracil;
D-glucosamine;
tissue distribution;
kidney targeting
- From:
The Chinese Journal of Clinical Pharmacology
2017;33(22):2278-2281
- CountryChina
- Language:Chinese
-
Abstract:
Objective To synthesize a derivative of 5-fluorouracil (5-FU) modified by D-glucosamine(Glc) and preliminarily investigate the biodistribution profile of the derivative in mice.Methods 5-FU-D-Glc was synthesized by conjugating 5-fluorouracil and D-glucosamine via an amide bond.The quantitative measurement of 5-FU and its derivative was established by HPLC in vitro and in vivo.Stabilities of 5-FU-D-Glc were investigated in phosphate buffer (pH7.4),freshly prepared mouse plasma and kidney homogenates,respectively.Tissue distributions of 5-FU and 5-FU-D-Glc were monitored by HPLC after drugs were intravenously administrated to mice.Results The chemical structures of target compound was confirmed by 1H-NMR,13C-NMR and LC-MS.The 5-FU-D-Glc showed a good stability under all given conditions with no substantial hydrolysis(＜ 10％).After intravenous administration to mice by caudal vein,the AUC0-t of 5-FU-D-Glc achieved in kidney was (9680.07 ± 330.20) μg · g-1 · min,which was enhanced by 20.3 fold compared with that of 5-FU.Meanwhile,the relative uptake efficiency (RE) and concentration efficiency (CE) were 21.27 and 10.45 respectively.Moreover,remarkably enhanced drug distribution and prolonged blood circulation time in plasma were found in 5-FU-D-Glc.Conclusion 5-fluorouracil-D-glucosamine derivative showed a good stability profile in vitro.The in vivo results highlighted a significant improvement of the kidney -tageted delivery of 5-FU by linked with D-glucosamine.
