Pharmacokinetics and tissue distribution of a water-soluble flavonol triglycoside, CTN986, in mice
Pharmacokinetics and tissue distribution of a water-soluble flavonol triglycoside, CTN986, in mice
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水溶性黄酮醇三糖苷 CTN986 在小鼠体内的药代动力学和组织分布
DOI：
10.1055/s-2008-1034307
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发表时间：
2008-02-01
期刊：
影响因子：
2.7
通讯作者：
Zhao, Yimin
中科院分区：
文献类型：
--
作者：
Guo, Jifen;Meng, Fanhua;Zhao, Yimin
CTN 986是一种高度水溶性的黄酮醇三糖苷，显示出令人感兴趣的抗抑郁作用，其药代动力学和生物利用度在小鼠静脉内（i. v.）腹膜内（i. p.）和口服给药。通过经验证的LC/MS/MS方法测定生物样品中CTN 986的浓度。采用非房室方法进行药代动力学数据分析。CTN 986的剂量依赖性药代动力学特征在i. v.给药（0.16、0.4和1.0 mg/kg）。静脉给药后，清除率（CL）随剂量增加无显著差异[252.66 +/- 42.82 mL/h（0.16 mg/kg）vs 241.73 +/- 14.93 mL/h（1.0 mg/ kg）]。CTN 986腹腔给药和口服给药的绝对生物利用度分别为96.57%和1.31%。CTN 986在小鼠体内分布广泛，给药后10 min，各组织浓度由高到低依次为十二指肠、胃、小肠、肾、肺、肝、脑、心、脾。总之，CTN 986在小鼠体内可以以完整形式吸收并广泛分布到组织中。
The pharmacokinetics and bioavailability of CTN986, a highly water-soluble flavonol triglycoside that has shown interesting antidepressant effects, were determined in mice after intravenous (i.v.), intraperitoneal (i.p.) and oral administrations. Concentrations of CTN986 in the biological samples were determined by a validated LC/MS/MS method. Non-compartmental methods were used to perform pharmacokinetic data analysis. The dose-dependent pharmacokinetics of CTN986 was characterized after i. v. administrations (0.16, 0.4 and 1.0 mg/kg) to mice. There was no significant difference in clearance (CL) with increasing dose [252.66 +/- 42.82 mL/h (0.16 mg/kg) versus 241.73 +/- 14.93 mL/h (1.0 mg/ kg)] after i.v. administrations. The absolute bioavailability of CTN986 after i.p. and Oral administrations was 96.57% and 1.31%, respectively. CTN986 was found to distribute widely in the internal organs of mice 10 min after Oral dosage, with tissue concentrations in the Order of duodenum, stomach, small intestine, kidney, lung, liver, brain, heart and spleen (from the highest to the lowest). In conclusion, CTN986 could be absorbed and extensively distributed into tissues as its intact form in mice.