St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats
- Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan (China)
- School of Pharmacy, China Medical University, Taichung, Taiwan (China)
St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 and 150 mg/kg of SJW, and 25 mg/kg of diclofenac, respectively. Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method. The results showed that 300 mg/kg of SJW significantly increased the AUC{sub 0−t} and C{sub max} of MTX by 163% and 60%, respectively, and 150 mg/kg of SJW significantly increased the AUC{sub 0−t} of MTX by 55%. In addition, diclofenac enhanced the C{sub max} of MTX by 110%. The mortality of rats treated with SJW was higher than that of controls. In conclusion, coadministration of SJW significantly increased the systemic exposure and toxicity of MTX. The combined use of MTX with SJW would need to be with caution. -- Highlights: ► St. John's wort significantly increased the AUC{sub 0−t} and C{sub max} of methotrexate. ► Coadministration of St. John's wort increased the exposure and toxicity of methotrexate. ► The combined use of methotrexate with St. John's wort will need to be with caution.
- OSTI ID:
- 22215879
- Journal Information:
- Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 263; ISSN TXAPA9; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Crystallization and preliminary crystallographic studies of Hyp-1, a St John’s wort protein implicated in the biosynthesis of hypericin
St. John's wort attenuates irinotecan-induced diarrhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis