The pharmacokinetics and tissue distribution of sinomenine in rats and its protein binding ability in vitro
The pharmacokinetics and tissue distribution of sinomenine in rats and its protein binding ability in vitro
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DOI：
10.1016/j.lfs.2005.05.054
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发表时间：
2005-11-04
期刊：
影响因子：
6.1
通讯作者：
Liu, L
中科院分区：
文献类型：
--
作者：
Liu, ZQ;Chan, K;Liu, L
本文研究了青藤碱在大鼠体内的药代动力学和组织分布，以及青藤碱在大鼠、兔血浆、白蛋白和α-1-酸性糖蛋白溶液中的结合能力。建立了测定青藤碱含量的高效液相色谱分析方法。结果表明，大鼠单次口服90 mg/kg青藤碱的生物利用度约为80%，其余药动学参数与静脉给药数据基本一致。这表明临床上口服青藤碱是合适的。大鼠灌胃给药后45min，内脏器官广泛分布，组织浓度由高到低依次为肾、肝、肺、脾、心、脑、睾丸。给药后90min，各脏器组织中药物浓度显著降低。肝脏和肾脏表现为主要器官，组织浓度较高，可能与青藤碱的代谢和消除有关。蛋白结合力测定表明，青藤碱在大鼠、兔血浆和白蛋白溶液中的蛋白结合率均在60%以上，而在α-1-酸性糖蛋白溶液中的蛋白结合率仅为33%左右。这一结果表明，由于青藤碱的酸性，它与白蛋白的结合能力可能比与α-L酸性糖蛋白的结合能力强得多。(C)2005 Elsevier Inc.保留所有权利。
Sinomenine, an alkaloid derived from the Chinese medical plant Sinomenium acutum, was studied with regard to its pharmacokinetics and tissue distribution in rats, and to its protein binding ability in the plasma of rats and rabbits and in the solutions of albumin and alpha-1-acid-glycoprotein. An HPLC analytical method was developed for determining sinomenine. The results demonstrated that oral administration with a single dosage at a rate of 90 mg sinomenine/kg in rats achieved about 80% bioavailability, while most of the other pharmacokinetic parameters were similar to the data from the animals treated intravenously. This indicates that oral administration of sinomenine would be appropriate in clinics. In rats, at 45 min after oral dosage, the drug was found to distribute widely in the internal organs, with tissue concentrations (from highest to lowest) in the order of kidneys, liver, lungs, spleen and heart, brain and testicles. At 90 min after dosing, the tissue concentrations in the organs were markedly decreased. The liver and kidneys manifested as the dominant organs with high tissue concentrations that might be responsible for metabolism and elimination of sinomenine. Examination of the protein binding ability showed that sinomenine with 4 mu g/ml concentration in the plasma of rats and rabbits or in the albumin solution achieved a protein binding rate of more than 60%, while in the solution of alpha-1-acid-glycoprotein the rate was only about 33%. This result suggests that sinomenine might have much more potent binding ability with albumin than with a-l-acid-glycoprotein, resulting from its acidic property. (c) 2005 Elsevier Inc. All rights reserved.