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Tuesday, June 29, 2021

Concomitant Use of High-dose Methotrexate and Glycyrrhizin Affects Pharmacokinetics of Methotrexate, Resulting in Hepatic Toxicity

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In Vivo. 2021 Jul-Aug;35(4):2163-2169. doi: 10.21873/invivo.12487.

ABSTRACT

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 e nzymes. 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.

PMID:34182493 | DOI:10.21873/invivo.12487

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