Effect of St John's wort (Hypericum perforatum) on cytochrome P-450 activity in perfused rat liver

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Authors

DOSTÁLEK Miroslav PISTOVČÁKOVÁ Jana JUŘICA Jan TOMANDL Josef LINHART Igor ŠULCOVÁ Alexandra HADAŠOVÁ Eva

Year of publication 2005
Type Article in Periodical
Magazine / Source Life Sciences
MU Faculty or unit

Faculty of Medicine

Citation
Field Pharmacology and pharmaceutical chemistry
Keywords St John's wort; cytochrome P450; perfused rat liver; drug interaction
Description St. John's wort (Hypericum perforatum) is a popular over-the-counter dietary supplement and a herbal antidepressant that has been implicated in drug interactions with substrates of several cytochrome P-450 (CYP) isozymes. The effects of the St. John's wort extract (100 mg/kg, i.p., once daily for 10 days) on metabolic activity of CYP450 were assessed in the system of isolated perfused rat liver. The substrates used in this study were tolbutamide (CYP2C6), dextromethorphan (CYP2D2) and midazolam (CYP3A2). Validated HPLC method was used to quantify all compounds of interest. St. John's wort administration affected CYP activity, causing a significant decline in AUC of dextromethorphan [F(4,31) = 1511, p < 0.001; PLSD, p < 0.001] and AUC of midazolam [F(3,25) = 221, p < 0.001; PLSD, p = 0.035] and a significant increase in AUC of tolbutamide [F(3,26) = 200, p < 0.001; PLSD, p < 0.001]. St. John's wort administration resulted in a significant induction of CYP2D2 and CYP3A2, and in a significant inhibition of CYP2C6 metabolic activities.
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