Research

Mechanisms Underlying Drug Diet Interactions

This project involves a unique collaboration between the fields of metabolism and natural products. In a project led by Dr. Mary Paine at the University of North Carolina at Chapel Hill and funded by the National Institute of General Medical Sciences, we are studying the mechanisms of drug-diet interactions. Essentially, we are partnering our skills in characterizing natural products with Dr. Paine’s skills in studying drug metabolism. While such metabolic studies are commonplace for drug-drug interactions, there are little data available on how the consumption of certain dietary substances (i.e. herbs, juices, foods) affect the metabolism of drugs, particularly in the gut. The challenge in this project is that, unlike most drug products, dietary substances are mixtures, composed of multiple, and often unknown, bioactive ingredients. My lab provides the natural products chemistry support that characterizes the dietary products under investigation.

mechanisms

Selected Publications:

“Isolation and Identification of Intestinal CYP3A Inhibitors from Cranberry (Vaccinium macrocarpon) Using Human Intestinal Microsomes.”
Eunkyung Kim, Arlene Sy-Cordero, Tyler N. Graf, Scott J. Brantley, Mary F. Paine, and Nicholas H. Oberlies
Planta Medica, 2011, 77, 265-270.
PMID:20717876; PMCID: PMC3023844; doi: 10.1055/s-0030-1250259

“The Warfarin-Cranberry Juice Interaction Revisited: A Systematic in Vitro-in Vivo Evaluation.”
Ngoc Ngo, Scott J. Brantley, Daniel R. Carrizosa, Angela D. M. Kashuba, E. Claire Dees, David J. Kroll, Nicholas H. Oberlies, and Mary F. Paine
Journal of Experimental Pharmacology, 2010, 2, 83-91.
PMID:20865058; PMCID: PMC2943398; doi: 10.2147/JEP.S11719

“Two Flavonolignans from Milk Thistle (Silybum marianum) Inhibit CYP2C9-Mediated Warfarin Metabolism at Clinically Achievable Concentrations.”
Scott J. Brantley, Nicholas H. Oberlies, David J. Kroll, and Mary F. Paine
Journal of Pharmacology and Experimental Therapeutics, 2010, 332, 1081-1087.
PMID:19934397; PMCID: PMC2835426; doi: 10.1124/jpet.109.161927

“Influence of Dietary Substances on Intestinal Drug Metabolism and Transport.”
Christina S. Won, Nicholas H. Oberlies, and Mary F. Paine
Current Drug Metabolism, 2010, 11, 778-792.
PMID: 21189136; PMCID: PMC3034088; http://www.benthamdirect.org/pages/content.php?CDM/2010/00000011/00000009/0006F.SGM

“Identification of a Cranberry Juice Product That Inhibits Enteric CYP3A-Mediated First-Pass Metabolism in Humans.”
Ngoc Ngo, Zhixia Yan, Tyler N. Graf, Daniel R. Carrizosa, Angela D. M. Kashuba, E. Claire Dees, Nicholas H. Oberlies, and Mary F. Paine
Drug Metabolism and Disposition, 2009, 37, 514-522.
PMID: 19114462; PMCID: PMC2650736; doi: 10.1124/dmd.108.024968