title: Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats.
abstract: 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 Blood samples were withdrawn via cardiopuncture at specific time points after drug administration.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(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.
authors.affiliation: Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Hsiu-Mei
authors.initials: HM
authors.lastname: Chiang
authors.forename: Shih-Hua
authors.initials: SH
authors.lastname: Fang
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Wen
authors.forename: Su-Lan
authors.initials: SL
authors.lastname: Hsiu
authors.forename: Shang-Yuan
authors.initials: SY
authors.lastname: Tsai
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Hou
authors.forename: Ying-Chang
authors.initials: YC
authors.lastname: Chi
authors.forename: Pei-Dawn Lee
authors.initials: PD
authors.lastname: Chao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001247:Asthenia / Q000139:chemically induced; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D041743:Herb-Drug Interactions; D007275:Injections, Intravenous; D007529:Isoflavones / Q000032:analysis / Q000737:chemistry; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015394:Molecular Structure; D010863:Piloerection / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D029908:Pueraria / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007529:Isoflavones; D010936:Plant Extracts; D008727:Methotrexate