This proposal will develop analytical methodology to identify key metabolic pathways and the metabolizing enzymes of botanicals responsible for drug interactions. Initially we will focus on the main active ingredients of widely used botanicals, green tea (epigallocatechin gallate), St. John's wort (hypericin and hyperforin), and milk thistle weed (silybin). Metabolism of these compounds will be investigated in vitro in liver microsomes and expressed human enzymes. Liquid chromatography coupled with tandem mass spectrometry will be used to identify the phase I metabolites. The cytochrome P450 isoforms will be identified using chemical inhibitor probes and specific expressed enzymes. Enzyme kinetic and inhibition parameters of these compounds will be evaluated to predict the interactions with known drugs. A web-accessible, interactive relational database will be developed to include the findings such as specific isoforms, metabolites formed, metabolic reactions and enzyme kinetics and the inhibition constants of the above standards. The database will be expanded in Phase II to also include in vivo data of botanical extracts and their synergistic effects to provide information to pharmacists and physicians.

Proposed Commercial Applications

The procedures and automated methods developed in these studies will be used to provide contract research services to pharmaceutical/botanical industry. The research will result is a database that could be sold to healthcare professionals and pharmaceutical industry.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43AT000792-01
Application #
6403121
Study Section
Special Emphasis Panel (ZRG1-SSS-6 (10))
Program Officer
Fu, Yali
Project Start
2001-09-05
Project End
2002-07-31
Budget Start
2001-09-05
Budget End
2002-07-31
Support Year
1
Fiscal Year
2001
Total Cost
$91,514
Indirect Cost
Name
Bioanalytical Systems, Inc. (BASI)
Department
Type
DUNS #
040294803
City
West Lafayette
State
IN
Country
United States
Zip Code
47906