THE EFFECTS OF GENOTYPE ON DRUG RESPONSE

这个子项目是众多研究子项目之一

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.