Adverse effects by artificial grapefruit seed extract products in patients on warfarin therapy
| Autor: | Torgny Rundlöf, Ann-Kristin Arvidsson, Gunilla Brenning, Olle Myrberg, Helena Brandin |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Magnetic Resonance Spectroscopy Grapefruit seed extract chemistry.chemical_compound Cytochrome P-450 Enzyme System Citrus paradisi Botany Cytochrome P-450 CYP3A Humans Drug Interactions Pharmacology (medical) International Normalized Ratio Adverse effect CYP2C9 Cytochrome P-450 CYP2C9 Pharmacology Polymorphism Genetic Natural product Traditional medicine CYP3A4 Plant Extracts Chemistry Benzethonium chloride Anticoagulants food and beverages General Medicine Middle Aged Seeds Benzethonium Female Aryl Hydrocarbon Hydroxylases Warfarin |
| Zdroj: | European Journal of Clinical Pharmacology. 63:565-570 |
| ISSN: | 1432-1041 0031-6970 |
| DOI: | 10.1007/s00228-007-0289-1 |
| Popis: | Grapefruit seed extract (GSE) is promoted as a natural product with antibacterial and antiviral properties. The aim of this study was to investigate the composition of some commercially available GSE products and evaluate their effect in vitro on two cytochrome P450 enzymes, CYP2C9 and CYP3A4.A couple on lifelong treatment with warfarin and continuous regular follow-ups took some drops of a GSE product for 3 days. The female patient experienced a minor subcutaneous haematoma 3 days later, and her international normalised ratio (INR) value was 7.9. This was reported to the Swedish Medical Products Agency (MPA) as a spontaneous post-marketing report concerning adverse drug reactions/interactions. The composition of the GSE products was determined by proton and carbon-13 nuclear magnetic resonance spectroscopy (NMR). The inhibitory effect of the GSE products on the cytochrome P450 enzymes was tested in an in vitro baculosome assay.The NMR analysis showed that all three investigated GSE products contained the synthetic preservative benzethonium chloride (BTC) in addition to glycerol and water. No authentic GSE extract was found in any of the three GSE products analysed. Furthermore, BTC was found to be a potent inhibitor of CYP3A4 and CYP2C9 activity in vitro.Our results suggest that BTC in the GSE products is responsible for the increase in the INR value in a patient on warfarin treatment. |
| Databáze: | OpenAIRE |
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