This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This project will examine the pharmacogenetics of flurbiprofen in the absence and presence of fluconazole. Flurbiprofen is a non-steriodal anti-inflammatory drug, similar to ibuprofen. Flubiprofen metabolism is a marker for the body's ability to metabolize drugs via the cytochrome P450 2C9 enzyme. Fluconazole, an anti-fungal drug, is an established inhibitor of metabolism by this same enzyme. It has also been established that individuals possessing the *3 genotype (genetic subtype) of cytochrome P450 2C9 have lower capacity to metabolize drugs like flurbiprofen than do individuals having the most common genotype (*1). Data from our laboratory suggest that individuals with the *3 genotype should also be less susceptible to inhibition of cytochrome P450 2C9 mediated metabolism of flurbiprofen than individuals with the *1 genotype. Thus, subjects will be screened for their individual cyrochrome P450 2C9 genotype and two subgroups identified (individuals possessing only the *1 subtype and individuals possessing a mixture of the *1/3* subtypes). We will study individuals with the *1/*3 genotypes (since the *3/*3 genotype is so rare in the population) and compare them to individuals with the most common genotype (*1/*1).
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