MECHANISMS UNDERLYING DRUG-DIET INTERACTIONS

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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. Similiar to the well published "grapefruit juice effect", ongoing studies are evaluating the interaction potential of other dietary substances on drug disposition. For example, GCRC 32354 investigated the effect of cranberry juice on fluvastatin metabolism and on the erythromycin breath test; subject enrollment and participation has been completed and the data have been evaluated. This study proposed in the present application is designed to determine whether the mechanism underlying the enhancement of the anticoagulative effect of warfarin by cranberry juice is due to inhibition of varfarin metabolism by the juice. A secondary objective is to determine whether cranberry juice elicits a grapefruit juice-type interaction with midazolam.