RT Journal Article
SR Electronic
T1 Concomitant Use of High-dose Methotrexate and Glycyrrhizin Affects Pharmacokinetics of Methotrexate, Resulting in Hepatic Toxicity
JF In Vivo
JO In Vivo
FD International Institute of Anticancer Research
SP 2163
OP 2169
DO 10.21873/invivo.12487
VO 35
IS 4
A1 KENTARO ABE
A1 TSUKASA HIGURASHI
A1 MIO TAKAHASHI
A1 AYAKO MAEDA-MINAMI
A1 YOHEI KAWANO
A1 SATORU MIYAZAKI
A1 YASUNARI MANO
YR 2021
UL http://iv.iiarjournals.org/content/35/4/2163.abstract
AB Background/Aim: High-dose methotrexate is a therapy for acute leukemia, malignant lymphoma, and osteosarcoma. Glycyrrhizin has been used to treat hepatic dysfunction caused by high-dose methotrexate. However, few studies have investigated the interaction between glycyrrhizin and high-dose methotrexate. Materials and Methods: Male Wistar rats were treated with high-dose methotrexate (500 or 1,000 mg/kg) alone, or with co-administration of 100 mg/kg glycyrrhizin. Plasma concentrations of methotrexate, alanine aminotransferase, aspartate aminotransferase, and total bilirubin were measured. Results: At both methotrexate doses, the blood concentration of methotrexate was significantly increased and total clearance was significantly reduced using co-administration of glycyrrhizin compared with methotrexate alone, which led to increased levels of hepatic enzymes. These results suggest that glycyrrhizin significantly increases the plasma level and delays the clearance of methotrexate, resulting in hepatic toxicity. Conclusion: The concomitant use of methotrexate and glycyrrhizin should be considered with caution.