St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4.
Clin Pharmacol Ther
; 68(6): 598-604, 2000 Dec.
Article
en En
| MEDLINE
| ID: mdl-11180019
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Plantas Medicinales
/
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP
/
Hypericum
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Sistema Enzimático del Citocromo P-450
/
Oxigenasas de Función Mixta
/
Intestino Delgado
/
Hígado
Límite:
Adult
/
Animals
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Humans
/
Male
Idioma:
En
Revista:
Clin Pharmacol Ther
Año:
2000
Tipo del documento:
Article
País de afiliación:
Suiza
Pais de publicación:
Estados Unidos