Inter-individual variability in pharmacokinetics and response to protease inhibitor-based antiretroviral therapy

药代动力学和对基于蛋白酶抑制剂的抗逆转录病毒治疗的反应的个体差异

• 批准号: G0800247/1
• 负责人: Andrew Owen
• 金额: $ 43.22万
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0800247%2F1
• 关键词: Inter; individual; variability; pharmacokinetics; response

Treatment for HIV clearly improves survival. However, some patients fail therapy either because of toxicity or because the virus mutates, allowing it to multiply even in the presence of the drug. Both of these factors are strongly influenced by the amount of drug that enters a patient?s bloodstream. For example, too much drug and the patient will experience some types of toxicity and too little drug and the virus is able to try out different mutations, eventually finding those which allow it to survive. Our knowledge of the factors that influence drug concentrations in the blood is rapidly developing. Our recent work has shown that SLCO transporters, which are molecular pumps that transfer anti-HIV drugs into gut and liver cells can influence the absorption and clearance of some drugs from the body. These transporters are encoded by the human genome and there are differences in these genes meaning that in some individuals they have different activity than in others. Therefore, the reason for this research is to assess whether differences in SLCO transporter genes are able to explain some of the differences in drug concentrations and susceptibility to toxicity and failure of anti-HIV drugs. Ultimately, if this project is successful it will aid the development of tests that help HIV doctors to give the right drug, at the right dose to the right patient.

艾滋病毒的治疗明显提高了存活率。然而，一些患者治疗失败，要么是因为毒性，要么是因为病毒发生了变异，即使在药物存在的情况下，病毒也会繁殖。这两个因素都受到进入患者体内的药物数量的强烈影响--S的血流。例如，太多的药物和患者将经历某些类型的毒性和太少的药物，病毒能够尝试不同的突变，最终找到那些允许它存活的突变。我们对影响血液中药物浓度的因素的了解正在迅速发展。我们最近的工作表明，SLCO转运体是将抗艾滋病毒药物转移到肠道和肝脏细胞的分子泵，可以影响一些药物在体内的吸收和清除。这些转运蛋白是由人类基因组编码的，这些基因存在差异，这意味着在一些个体中，它们的活动与其他人不同。因此，这项研究的目的是评估SLCO转运蛋白基因的差异是否能够解释抗HIV药物的药物浓度以及对毒性和失败的敏感性的一些差异。最终，如果这个项目成功，它将有助于开发测试，帮助艾滋病毒医生在正确的剂量给正确的患者开出正确的药物。