检索结果-南通市图书馆

Pharmacokinetics of sifuvirtide, a novel anti-HIV-1 peptide, in monkeys and its inhibitory concentration in vitro1

Acta Pharmacologica Sinica 2005年第10期26卷 1274-1280页

作者： Shu-jia DAI~2, Gui-fang DOU~3, Xiao-hong QIAN~(4,5), Hai-feng SONG~4, Zhong-ming TANG~2, De-sheng LIU~2, Xiu-wen LIU~2, Liu-meng YANG~6, Yong-tang ZHENG~6, Qing LIANG~7 ~2 Laboratory of Metabolism of Biotechnology Derived Drugs, Beijing Institute of Radiation Medicine, Beijing 100850 ~3 Laboratory of Drug Metabolism and Pharmacokinetics, Beijing Institute of Transfusion Medicine, Beijing 100850 ~5 Laboratories of Genomics and Proteomics, Beijing Institute of Radiation Medicine, Beijing 100850 ~6 Laboratory of Molecular hnmunopharmacology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 ~7 fusogen pharmaceuticals inc, tianjin 300051, china LaboratoryofMetabolismofBiotechnologyDerivedDrugs BeijingInstituteofRadiationMedicineBeijing100850 LaboratoryofDrugMetabolismandPharmacokinetics BeijingInstituteofTransfusionMedicineBeijing100850

Aim: To study the pharmacokinetics of sifuvirtide, a novel anti-human immunodeficiency virus （HIV） peptide, in monkeys and to compare the inhibitory concentrations of sifuvirtide and enfuvirtide on HIV-1-infected-cell fusion. Methods: Monkeys received 1.2 mg/kg iv or sc of sifuvirtide. An on-line solid-phase extraction procedure combined with liquid chromatography tandem mass spectrometry （SPELC/MS/MS） was established and applied to determine the concentration of sifuvirtide in monkey plasma. A four-127I iodinated peptide was used as an internal standard. Fifty percent inhibitory concentration (IC50) of sifuvirtide on cell fusion was determined by co-cultivation assay. Results: The assay was validated with good precision and accuracy. The calibration curve for sifuvirtide in plasma was linear over a range of 4.88-5000μg/L, with correlation coefficients above 0.9923. After iv or sc administration, the observed peak concentrations of sifuvirtide were 10 626±2 886μg/L and 528±191μg/L, and the terminal imination half-lives (T1/2) were 6.3±0.9 h and 5.5±1.0 h, respectively. After sc, Tmaxwas 0.25-2h, and the absolute bioavailability was 49%±13%. Sifuvirtide inhibited the syncytium formation between HIV-1 chronically infected cells and uninfected cells with an IC50of 0.33μg/L. Conclusion: An on-line SPE-LC/MS/MS approach was established for peptide pharmacokinetic studies. Sifuvirtide was rapidly absorbed subcutaneously into the blood circulation. The T1/2of sifuvirtide was remarkably longer than that of its analog, enfuvirtide, reported in healthy monkeys and it conferred a long-term plasma concentration level which was higher than its IC50in vitro.

关键词： sifuvirtide pharmacokinetics HIV HIV fusion inhibitors enfuvirtide on-line solid-phase extraction macaque

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：