甘草酸与大剂量甲氨蝶呤合用影响甲氨蝶呤的药代动力学，导致肝毒性。
Concomitant Use of High-dose Methotrexate and Glycyrrhizin Affects Pharmacokinetics of Methotrexate, Resulting in Hepatic Toxicity.
机构信息
Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
Department of Pharmacy, National Cancer Center Hospital, Tokyo, Japan.
出版信息
In Vivo. 2021 Jul-Aug;35(4):2163-2169. doi: 10.21873/invivo.12487.
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.
背景/目的：大剂量甲氨蝶呤是治疗急性白血病、恶性淋巴瘤和骨肉瘤的一种疗法。甘草酸已被用于治疗大剂量甲氨蝶呤引起的肝损伤。然而，很少有研究调查甘草酸与大剂量甲氨蝶呤之间的相互作用。
材料和方法
雄性 Wistar 大鼠单独给予大剂量甲氨蝶呤（500 或 1000mg/kg），或同时给予 100mg/kg 甘草酸。测量血浆中甲氨蝶呤、丙氨酸氨基转移酶、天冬氨酸氨基转移酶和总胆红素的浓度。
结果
在两种甲氨蝶呤剂量下，与单独使用甲氨蝶呤相比，同时使用甘草酸会显著增加甲氨蝶呤的血药浓度，并显著降低总清除率，导致肝酶水平升高。这些结果表明，甘草酸显著增加了甲氨蝶呤的血浆水平并延迟了其清除，导致肝毒性。
结论
应谨慎考虑同时使用甲氨蝶呤和甘草酸。
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