Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats

Journal Article · Wed Dec 14 23:00:00 EST 2005 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2005.04.015· OSTI ID:20783390

Chiang, H -M ^[1]; Fang, S -H ^[2]; Wen, K -C ^[3]; Hsiu, S -L ^[4]; Tsai, Shang-Yuan ^[4]; Hou, Y -C ^[5]; Chi, Y -C ^[1]; Lee Chao, Pei-Dawn ^[4]

---

1. Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan (China)
2. School of Medicine, China Medical University, Taichung, Taiwan (China)
3. School of Cosmeceutics, China Medical University, Taichung, Taiwan (China)
4. School of Pharmacy, China Medical University, Taichung, Taiwan (China)
5. School of Chinese Medicine, China Medical University, Taichung, Taiwan (China)

Isoflavone supplements are nowadays widely used as alternative for hormone replacement therapy. However, the safety remains unanswered. This study attempted to investigate the effect of Pueraria lobata root decoction (PLRD), an isoflavone-rich herb, on the pharmacokinetics of methotrexate (MTX), a bicarboxylate antimetabolite with narrow therapeutic window. Rats were orally and intravenously given methotrexate alone and coadministered with PLRD. Blood samples were withdrawn via cardiopuncture at specific time points after drug administration. Serum methotrexate concentrations were assayed by specific monoclonal fluorescence polarization immunoassay method. Pharmacokinetic parameters were calculated using noncompartment model of WINNONLIN for both oral and intravenous data of MTX. Our results showed that coadministration of 4.0 g/kg and 2.0 g/kg of PLRD significantly increased the AUC{sub 0-t} by 207.8% and 127.9%, prolonged the mean residence time (MRT) by 237.8 and 155.2%, respectively, finally resulted in surprisingly high mortalities of 57.1% and 14.3% in rats. When MTX was given intravenously, the coadministration of PLRD at 4.0 g/kg significantly increased the half-life by 53.9% and decreased the clearance by 47.9%. In conclusion, the coadministration of PLRD significantly decreased the elimination and resulted in markedly increased exposure of MTX in rats.

• OSTI ID: 20783390
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 209; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BLOOD
CLEARANCE
FLUORESCENCE
HALF-LIFE
HERBS
HORMONES
IMMUNOASSAY
METHOTREXATE
MORTALITY
POLARIZATION
RATS
SAFETY