St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats.
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 25mg/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 Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method.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(0-t) and C(max) of MTX by 163% and 60%, respectively, and 150 mg/kg of SJW significantly increased the AUC(0-t) of MTX by 55%. In addition, diclofenac enhanced the C(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.
Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan.
Shih-Ying
SY
Yang
Shin-Hun
SH
Juang
Shang-Yuan
SY
Tsai
Pei-Dawn Lee
PD
Chao
Yu-Chi
YC
Hou
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D004347:Drug Interactions; D020902:Hypericum / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D010936:Plant Extracts / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D010936:Plant Extracts; D004008:Diclofenac; D008727:Methotrexate