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Abstract
Grant Number: 5F31AT003973-03 Project Title: Curcumin-piperine interaction with CYP3A, UGT, and SULT enzymes.
PI Information: Name Title VOLAK, LAURIE PAULINE. laurie.volak@tufts.edu Abstract: DESCRIPTION (provided by applicant): The use of complementary and alternative medicines has increased dramatically over the past decade as the benefits of these natural medications are realized. Although herbal medicines are commonly believed to be a safer alternative to traditional medications, physicians are increasingly concerned about interactions between these medications. One reason for this concern is that unlike traditional medications, safety and drug interaction data is not required by the FDA prior to the sale of herbal supplements to consumers. Often, such interactions are only discovered after a serious and sometimes life-threatening event has occurred. Curcumin, an herbal supplement of recent clinical interest, is in clinical trials for the treatment of several advanced cancers and Alzheimer's disease. However, limited data has been generated examining curcumin's potential for drug-herb interactions due to inhibition of the major drug metabolizing enzymes. Prior to the broader therapeutic application of curcumin, curcumin's potential for these drug-herb interactions should be investigated. Here, we propose to test the effect of curcumin on the in vitro metabolism of midazolam and acetaminophen, index substrates for phase I (cytochrome P450 isoform CYP3A) and phase II (UDP-glucuronosyltransferase and sulfotransferase) drug metabolism, respectively. Curcumin, due to its limited bioavailability, is often administered with a bioavailability enhancing agent, piperine, which may increase the likelihood of curcumin to cause drug-herb interactions. Therefore, we also propose to test the effect of piperine and a combination of curcumin-piperine on midazolam and acetaminophen metabolism in vitro. Furthermore, we will verify our in vitro results with an in vivo clinical study examining the effects of a curcumin-piperine combination on the pharmacokinetics of a single dose of acetaminophen or midazolam in a randomized 4-way crossover study in healthy volunteers. The results from this study will provide important information on the potential of curcumin-piperine to inhibit the metabolism of co-administered drugs and cause drug-herb interactions. Ultimately, this information can be used by physicians to help guard patients from potentially unsafe combinations of herbal and traditional medicines.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
acetaminophen, enzyme, metabolism
Alzheimer's disease, acid, adenocarcinoma, alternative medicine, ascorbate, base, bilirubin, blood, capsaicin, carotene, cell, cell line, clinical trial, colon, cystic fibrosis, cytochrome P450, drug interaction, drug metabolism, glucuronosyltransferase, human, indexing, infection, intestine, kidney, lead, liver, malaria, medicine, microsome, midazolam, model, motivation, mycophenolic acid, neoplasm /cancer, nitrophenol, oxidation, pharmacokinetics, physician, psychomotor function, selenium, sulfation, sulfotransferase, triazolam, urine, verapamil, volunteer
clinical research
Institution: TUFTS UNIVERSITY BOSTON Office of the Vice Provost BOSTON, MA 02111 Fiscal Year: 2008 Department: PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Project Start: 25-SEP-2006 Project End: 24-SEP-2009 ICD: NATIONAL CENTER FOR COMPLEMENTARY & ALTERNATIVE MEDICINE IRG: ZAT1