Effect of St John's wort (Hypericum perforatum) on cytochrome P-450 activity in perfused rat liver.
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.
Dostalek
M
M
Masaryk University, Faculty of Medicine, Department of Pharmacology, Tomesova 12, 60200 Brno, Czech Republic. mdostal@med.muni.cz
Pistovcakova
J
J
Jurica
J
J
Tomandl
J
J
Linhart
I
I
Sulcová
A
A
Hadasova
E
E
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D019540:Area Under Curve; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D003915:Dextromethorphan / Q000493:pharmacokinetics; D041743:Herb-Drug Interactions; D020902:Hypericum; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008874:Midazolam / Q000493:pharmacokinetics; D010477:Perfusion; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014044:Tolbutamide / Q000493:pharmacokinetics
D000928:Antidepressive Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; C422326:Hypericum extract LI 160; D010936:Plant Extracts; D003915:Dextromethorphan; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; D008874:Midazolam