hLAT1和P-gp对Asp-DOX药代动力学性质影响的研究

来源 :2015第11届全国药物和化学异物代谢学术会议 | 被引量 : 0次 | 上传用户：cuileidan

【摘要】

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【作者】

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武卫党慈小燕李亚卓高晶曾勇李薇魏滋鸿董艳伊秀林刘昌孝

【机构】

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天津药物研究院新药安全评价有限公司,天津300193 天津医科大学药学院,天津300070

【出处】

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2015第11届全国药物和化学异物代谢学术会议

【发表日期】

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2015年9期

【关键词】

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Asp-DOX LAT1 P-gp 药物转运体药代动力学

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　　建立了体内外hLAT1和P-gp药物转运体药理学模型,研究了LAT1和P-gp两种药物转运体对化合物Asp-DOX及原形对照药DOX药代动力学的影响,通过荧光显微镜和荧光HPLC检测方法：,观察和测定了Asp-DOX和DOX在细胞和组织中的含量.结果：显示,Asp-DOX在LAT1过表达肿瘤细胞的体外吸收量较DOX提高了3倍多(p＜0.05)；Asp-DOX在血液中的半衰期t1/2较DOX明显延长,AUC也较DOX增加了8倍多；Asp-DOX在HepG2和HCT116肿瘤组织中的含量都分别比原型药DOX提高了2.2倍和6.1倍多(P＜0.05).P-gp对对Asp-DOX的外排作用较DOX明显降低.hLAT1能够显著增加过量表达LAT1肿瘤细胞和肿瘤组织对Asp-DOX的吸收和分布；P-gp对Asp-DOX的外排作用较DOX显著降低.

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hLAT1和P-gp对Asp-DOX药代动力学性质影响的研究

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