Pharmacokinetics of SN-38 in rats and tissue distribution of 7-ethyl-10-hydroxycamptothecin in mice after intravenous injection of irinotecan hydrochloride nanoparticles.
- Author:
Fu-Ying YANG
;
Wen-Ping ZHANG
;
Xin-Yu WANG
;
Wen-Cheng YANG
;
Hong-Wan DANG
- Publication Type:Journal Article
- MeSH:
Animals;
Antineoplastic Agents, Phytogenic;
pharmacokinetics;
Camptothecin;
analogs & derivatives;
pharmacokinetics;
Chromatography, Liquid;
Colon;
metabolism;
Half-Life;
Injections, Intravenous;
Lung;
metabolism;
Mice;
Nanoparticles;
administration & dosage;
Rats;
Tandem Mass Spectrometry;
Tissue Distribution
- From:
Acta Pharmaceutica Sinica
2014;49(7):1029-1033
- CountryChina
- Language:Chinese
-
Abstract:
The paper reported an investigation of the pharmacokinetics of SN-38 (7-ethyl-10-hydroxy-camptothecin) in rats and the tissue distribution in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11) via tail veins. An LC-MS/MS method was established to determine the concentrations of SN-38 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of SN-38 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with irinotecan solution, the elimination half-life of SN-38 was prolonged from 2.17 h to 2.67 h after the intravenous injection of CPT-11 NPs, but its AUC had little change. After the injection of CPT-11 NPs in mice, over time, the concentrations of CPT-11-metabolized SN-38 in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, followed by in the spleen and liver, but those in the heart and brain had no change. However, the amount of SN-38 in the kidneys was reduced with time. CPT-11 NPs could prolong SN-38's (one of its metabolites) blood circulation time in rats and significantly increased the concentration of CPT-11-metabolized SN-38 in the whole blood, colon and lungs of mice. CPT-11 NPs made SN-38 efficiently target-bind to the colon and lungs of mice.
