THE EFFECTS OF GENOTYPE ON DRUG RESPONSE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 大多数代谢药物依赖于细胞色素P450家族的酶从体内消除。此外，依赖于ATP的转运体，如P-糖蛋白，也是药物分布和消除的重要决定因素。最近在编码细胞色素P450和药物转运蛋白的基因中发现的单核苷酸多态表明，遗传多样性有助于药物药代动力学和反应的个体间差异。我们以前已经获得了大量志愿者的表型数据，现在建议对这些人进行基因分型，以揭示遗传多样性对咪达唑仑等探测药物的药代动力学的贡献，以及对克拉霉素和利福平等抑制剂和诱导剂之间的药物相互作用的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The majority of metabolized drugs are dependent on the cytochrome P450 family of enzymes for elimination from the body. In addition, ATP dependent transporters, such as p-glycoprotein, are also important determinants of drug distribution and elimination. Recent discoveries of single nucleotide polymorphisms in the genes that code for cytochrome P450s and drug transporters have suggested that genetic diversity contributes to interindividual variability in drug pharmacokinetics and response. We have previously obtained phenotypic data in a large number of volunteers and now propose to genotype these same individuals to reveal the contribution of genetic diversity to the pharmacokinetics of probe drugs, such as midazolam, and to drug-drug interactions with inhibitors and inducers, such as clarithromycin and rifampin.