Document Detail


Variability in PXR-mediated induction of CYP3A4 by commercial preparations and dry extracts of St. John's wort.
MedLine Citation:
PMID:  17593354     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
St. John's wort (SJW, Hypericum perforatum) is a well-tolerated herbal medicine widely used for the treatment of mild and moderate depressions. In the last 5 years, SJW has been implicated in drug interactions, which are largely mediated by the induction of the drug metabolizing enzymes, especially CYP3A4. There is still some controversy regarding the exact mechanism of induction and the identity of the SJW constituents involved. We investigated in LS174T cells the induction of CYP3A4 by ten SJW extracts, six commercial preparations, and the purified SJW constituent hyperforin. The content of hyperforin among the commercial preparations of SJW varied 62-fold (range 0.49-30.57 mg/dose). The CYP3A4 induction was mediated by PXR, but not by CAR. The magnitude of the induction correlated statistically significantly with the content of hyperforin in commercial SJW preparations (R = 0.87, p = 0.004) and in dry extracts (R = 0.65, p = 0.03), but not with their content of flavonoids or hypericin. Most of the CYP3A4 induction response occurred in the hyperforin range encountered in the blood of patients treated with SJW preparations. A temperature-induced decrease in the hyperforin content of a selected dry SJW extract abolished the induction of CYP3A4. In conclusion, commercial SJW preparations still exhibit an enormous variability in CYP3A4 induction, which is mediated by hyperforin and PXR. SJW preparations with lower hyperforin content should reduce the frequency of clinical interactions involving this herbal drug.
Authors:
Ute Gödtel-Armbrust; Annegret Metzger; Ulrike Kroll; Olaf Kelber; Leszek Wojnowski
Related Documents :
3954114 - Neonatal responses to alphaprodine administered during labor.
10432144 - Preterm labor: placental pathology and clinical correlation.
11100294 - How to diagnose preterm labor: a clinical dilemma.
3276074 - Reversal of acute polyhydramnios after fetal renal decompression.
8582714 - Corticosteroid-binding globulin in preterm infants in an intensive care unit.
6987464 - Results of repair of coarctation of the aorta during infancy.
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-26
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  375     ISSN:  0028-1298     ISO Abbreviation:  Naunyn Schmiedebergs Arch. Pharmacol.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-07-19     Completed Date:  2007-12-06     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  377-82     Citation Subset:  IM    
Affiliation:
Institut für Pharmakologie, Johannes Gutenberg Universität, Obere Zahlbacher Str. 67, 55131 Mainz, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Bicyclo Compounds / analysis
Chromatography, High Pressure Liquid
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System / biosynthesis*
Dose-Response Relationship, Drug
Flavonoids / analysis
Humans
Hypericum*
Perylene / analogs & derivatives*,  pharmacology
Phloroglucinol / analogs & derivatives,  analysis
Plant Extracts / chemistry,  pharmacology
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Steroid / genetics,  physiology*
Response Elements
Tablets
Terpenes / analysis
Transcription Factors / genetics
Transfection
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Bicyclo Compounds; 0/Flavonoids; 0/Plant Extracts; 0/Receptors, Cytoplasmic and Nuclear; 0/Receptors, Steroid; 0/Tablets; 0/Terpenes; 0/Transcription Factors; 0/constitutive androstane receptor; 0/pregnane X receptor; 108-73-6/Phloroglucinol; 11079-53-1/hyperforin; 198-55-0/Perylene; 548-04-9/hypericin; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.13.67/CYP3A4 protein, human; EC 1.14.14.1/Cytochrome P-450 CYP3A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Pharmacological evidence for altered src kinase regulation of I (Ca,L) in patients with chronic atri...
Next Document:  Intracerebroventricular administration of nitric oxide-sensitive guanylyl cyclase inhibitors induces...