St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4.

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Durr D, Stieger B, Kullak-Ublick GA, Rentsch KM, Steinert HC, Meier PJ, Fattinger K

St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4.

Clin Pharmacol Ther. 2000 Dec;68(6):598-604.

PubMed ID

11180019 [ View in PubMed

]

Abstract

BACKGROUND: St John's Wort (hypericum perforatum) is an herbal medicine that is frequently used for therapy of mild depression. Recently, St John's Wort was reported to substantially decrease blood/plasma concentrations and efficacy of cyclosporine (INN, ciclosporin), indinavir, and digoxin. In this study we investigated the mechanisms of these St John's Wort-induced drug interactions. METHODS AND RESULTS: In a preclinical study, the administration of St John's Wort extract to rats during 14 days resulted in a 3.8-fold increase of intestinal P-glycoprotein/Mdrl expression and in a 2.5-fold increase in hepatic CYP3A2 expression (Western blot analyses). In a clinical study, the administration of St John's Wort extract to 8 healthy male volunteers during 14 days resulted in an 18% decrease of digoxin exposure after a single digoxin dose (0.5 mg), in 1.4- and 1.5-fold increased expressions of duodenal P-glycoprotein/MDR1 and CYP3A4, respectively, and in a 1.4-fold increase in the functional activity of hepatic CYP3A4 (14C-erythromycin breath test). CONCLUSIONS: These results indicate direct inducing effects of St John's Wort on intestinal P-glycoprotein/MDR1 (in rats and humans), hepatic CYP3A2 (in rats), and intestinal and hepatic CYP3A4 (in humans). Therefore the results provide a mechanistic explanation for the previously observed drug interactions in patients and support the importance of intestinal P-glycoprotein/MDR1 in addition to intestinal and hepatic CYP3A4 for overall drug absorption and disposition in humans.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
St. John's Wort	P-glycoprotein 1	Protein	Humans	Unknown	Inducer	Details

Drug Interactions

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drugs	Interaction
Integrate drug-drug interactions in your software
Atazanavir St. John's Wort	The serum concentration of Atazanavir can be decreased when it is combined with St. John's Wort.
Guanfacine St. John's Wort	The serum concentration of Guanfacine can be decreased when it is combined with St. John's Wort.
Lapatinib St. John's Wort	The serum concentration of Lapatinib can be decreased when it is combined with St. John's Wort.
Nifedipine St. John's Wort	The serum concentration of Nifedipine can be decreased when it is combined with St. John's Wort.
Paliperidone St. John's Wort	The serum concentration of Paliperidone can be decreased when it is combined with St. John's Wort.