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Rosita Rodriguez-Proteau
Associate Professor, College of Pharmacy
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RESEARCH:
Drug Metabolism by Intestinal Flavin Monooxygenases (FMOs)
Characterization of intestinal FMOs in human duodenum, jejunum, ileum, colon, and in continuous cell lines from intestinal and colonic origin are being investigated. Human intestinal FMOs are being evaluated for the presence of FMO protein and FMO catalytic activity. Also, direct inhibitory or stimulatory effects of flavonoids are being evaluated using cDNA-expressed human FMOs. Thus, this project will contribute to the knowledge of human intestinal metabolism as well as provide an understanding of the effect of dietary flavonoids on intestinal FMO-mediated metabolism of orally administered therapeutic drugs within the various regions of the digestive tract.
Drug-Dietary Flavonoid Intestinal Absorption Interaction
The hypothesis of this study is that exposure of humans to dietary flavonoids can influence drug absorption by altering the P-glycoprotein (Pgp)-dependent or Pgp-independent transport mechanisms (drug-dietary interactions). To test the hypothesis, studies are being conducted to evaluate the role of the free flavonoids (predominant form after intestinal microflora hydrolysis of the glycosylated flavonoid), genistein, naringenin, quercetin, and epigallocatechin gallate, on Pgp-dependent (3H-digoxin and 3H-cyclosporin A) and Pgp-independent transport (3H-tamoxifen and 3H-cimetidine) mechanisms. Also, because the flavonoids generally occur in plants as the glycosylated derivatives, studies are also being conducted on the influence of glycosylated flavonoids, genistin, naringin, and quercitrin, on Pgp-dependent (3H-digoxin and 3H-cyclosporin A) and Pgp-independent transport (3H-tamoxifen and 3H-cimetidine) mechanism.
Genetic Determinants of Intestinal Drug Absorption
The expression of variant alleles associated with drug absorption and metabolism are often correlated to ethnicity. The hypotheses of these studies are: i) that the expression of variant alleles associated with drug absorption and metabolism, which are often correlated to ethnicity, can enhance or reduce intestinal transporter and metabolic activity; ii) that gender differences can enhance or reduce intestinal transporter and metabolic activity; and iii) that the expression of intestinal transporters and enzymes varies within the intestine. Thus, ethnicity, gender, and intestinal region may have a profound effect on the efficacy and/or toxicity of therapeutic drugs and on susceptibility to xenobiotic-induced diseases.