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新型钾通道开放剂(QO-58)在大鼠体内组织分布研究
  • 期刊名称:中国药理学通报
  • 时间:0
  • 页码:00-00
  • 语言:中文
  • 分类:R-332[医药卫生] R969.1[医药卫生—药理学;医药卫生—药学]
  • 作者机构:[1]河北医科大学药理教研室,教育部血管与神经生物重点实验室,河北省新药药理毒理重点实验室,河北石家庄050017, [2]邢台医学高等专科学校药剂教研室,河北邢台054000
  • 相关基金:国家自然科学基金(No NSFC 30970659); 教育部新世纪优秀人才支持计划(No NCET 09-0116) 教育部重点研究课题(No 208014); 河北省卫生厅重点课题(No 20100034)资助项目
  • 相关项目:细胞膜受体调节M/KCNQ钾离子通道功能的分子机制的研究
中文摘要:

目的建立大鼠组织中QO-58浓度的测定方法,并研究其组织分布。方法 SD大鼠灌胃给药QO-58(50 mg.kg-1)后,于给药后2、7、18、36 h断头放血处死大鼠,立即取出各脏器组织,滤纸吸干浮血,称重后用2倍量乙腈制成匀浆,取组织匀浆液用乙腈处理,以C18色谱柱Shim-pack VP-ODS C18(250 mm×4.6 mm,5μm)为固定相,选择285 nm为检测波长,流动相为乙腈:0.2 mol.L-1乙酸铵(45∶55),尼群地平为内标,柱温35℃,用HPLC法测定各组织中QO-58药物浓度。比较各组织的QO-58浓度,分析药物在大鼠体内的分布情况。结果大鼠灌胃给予QO-58 50 mg.kg-1后,肝脏中药物浓度最高,其次在肺、小肠、肾和胃等组织浓度较高,在肌肉、脂肪、脑、睾丸中浓度较低。大多数组织在7 h药物浓度达高峰,然后逐渐下降,36 h时大部分组织中检测不到QO-58。结论 QO-58主要分布在肝脏、小肠、肾和胃等组织,脂肪、脑、睾丸中分布量少;在所研究的组织中,未见明显的特殊蓄积现象。

英文摘要:

Aim To develop a sensitive,specific and accurate method for quantifying QO-58 in rat tissues to investigate the tissue distribution of QO-58 in rats.Methods SD rats were killed by exsanguination at 2,7,18 and 36 h after a single oral administration with one dose of QO-58(50 mg·kg-1).The tissues were taken out and went on the next procedure: to blot the surface blood with filter paper,to make into homogenates preparation with double weight of acetonitrile and the concentrations of QO-58 in the tissues were determined by HPLC method.Results The highest level was observed in liver,then in kidney,intestine,stomach and lungs.But the levels of brain,fat,testis,uterus were lower.The drug seemed not accumulate in rats.Conclusion The method is shown to be accurate,convenient and suitable for preclinical tissue distribution studies of QO-58.Liver,kidney,intestine,stomach and lung were major distribution tissues of QO-58 in rats.Also there is no long-term accumulation of QO-58 in rat tissues.

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