MDR-1-INHIBITION AND CYP3A ACTIVITY

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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. Our hypothesis is that MDR1 activity may affect the ERBT but not the midazolam clearance, and thus confound CYP3A assessment by the ERBT. The purpose of our study is to demonstrate that inhibition of MDR1 activity by the investigational MDR1 inhibitor tariquidar/XR-9576 (Xenova Ltd., UK) will affect the ERBT but not midazolam's disposition, possibly explaining the disparate results between these two assays for the determination of CYP3A activity.