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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Gorman, Gregory S. Coward, Lori Darby, Adrienne Rasberry, Bethany |
| Description | Country affiliation: United States Author Affiliation: Gorman GS ( McWhorter School of Pharmacy, Samford University, Birmingham, AL 35229, USA. ggorman@samford.edu) |
| Abstract | OBJECTIVES: The aim of this study was to investigate the impact of commercially available, over-the-counter herbal supplements (St John's wort, black cohosh and ginger root extract) on the metabolic activation of tamoxifen and irinotecan. METHODS: Co-incubation of each drug and supplement combination over a range of concentrations was conducted in human liver microsomes and the decrease in the rate of active metabolite formation was monitored using high-performance liquid chromatography tandem mass spectrometry. Data was analysed using non-linear regression analysis and Dixon plots to determine the dominant mechanism of inhibition and to estimate the Ki and IC50 values of the commercial supplements. KEY FINDINGS: The data suggest that black cohosh was the strongest inhibitor tested in this study for both CYP450 and carboxyesterase mediated biotransformation of tamoxifen and irinotecan, respectively, to their active metabolites. St John's wort was a stronger inhibitor compared with ginger root extract for tamoxifen (CYP mediated pathway), while ginger root extract was a stronger inhibitor compared with St John's wort for the carboxyesterase mediated pathway. CONCLUSIONS: Commercially available supplements are widely used by patients and their potential impact on the efficacy of the chemotherapy is often unknown. The clinical significance of these results needs to be evaluated in a comprehensive clinical trial. |
| File Format | HTM / HTML |
| ISSN | 00223573 |
| Issue Number | 7 |
| Volume Number | 65 |
| e-ISSN | 20427158 |
| Journal | Journal of Pharmacy and Pharmacology |
| Language | English |
| Publisher | Wiley |
| Publisher Date | 2013-07-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Pharmacology Camptothecin Analogs & Derivatives Enzyme Inhibitors Pharmacology Plant Extracts Tamoxifen Metabolism Antineoplastic Agents, Hormonal Administration & Dosage Antineoplastic Agents, Phytogenic Carboxylesterase Antagonists & Inhibitors Chromatography, High Pressure Liquid Cimicifuga Chemistry Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 Enzyme System Dose-response Relationship, Drug Drug Interactions Ginger Humans Hypericum Inhibitory Concentration 50 Microsomes, Liver Drug Effects Enzymology Regression Analysis Tandem Mass Spectrometry Comparative Study Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Pharmaceutical Science |
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