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. Using animal and in vitro models, we recently found that fasting results in induction of activity of CYP3A4, member of the hepatic cytochrome P450 enzymes. Our data further suggest that this activity is likely to occur in humans. Given the wide variability in dosing relative to time of food intake, our preclinical data suggest that the relationship between fasting/feeding and CYP3A4 activity could have broad implications for dosing as well as control of therapeutic and toxic effects of numerous pharmacologic agents. We propose to study the activity of CYP3A4 in fed and fasting normal volunteers through a tested and validated assay, the erythromycin breath test (ERBMT).
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