Nafamostat mesilate inhibits linezolid metabolism via its antioxidant effects
Nafamostat mesilate inhibits linezolid metabolism via its antioxidant effects
复制标题
甲磺酸萘莫司他通过其抗氧化作用抑制利奈唑胺代谢
DOI：
10.1111/1744-9987.13545
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发表时间：
2020
影响因子：
1.9
通讯作者：
Nishida Osamu
中科院分区：
文献类型：
--
作者：
Kuriyama Naohide;Matsumoto Kana;Morita Kunihiko;Shimomura Yasuyo;Hara Yoshitaka;Hasegawa Daisuke;Nakamura Tomoyuki;Yamashita Chizuru;Kato Yu;Komura Hidefumi;Nishida Osamu
接受肾脏替代治疗的患者通常表现出高血浆利奈唑胺浓度。利奈唑胺通过氧化代谢。甲磺酸萘莫司他具有抗氧化作用，在肾脏替代治疗期间经常用作抗凝剂。我们的目的是研究甲磺酸萘莫司他对血浆利奈唑胺浓度的影响。我们检查了利奈唑胺和萘莫司他的联合给药是否对血浆利奈唑胺浓度有影响。将小鼠随机分为两组（n = 18/组）：利奈唑胺（100mg kg−1，皮下注射） + nafamostat（30mg kg−1，腹腔注射）和利奈唑胺 + 生理盐水。 5小时时，利奈唑胺+萘莫司他联合给药组的利奈唑胺浓度显着高于利奈唑胺+生理盐水组（分别为20.6±9.8 vs 3.6±1.2 μg/mL，P<0.001）。萘莫司他的抗氧化作用可能会抑制利奈唑胺的代谢，如果在肾脏替代治疗期间同时服用两者，会导致利奈唑胺浓度过高的不良事件。
Patients who undergo renal replacement therapy often exhibit a high plasma linezolid concentration. Linezolid is metabolized via oxidation. Nafamostat mesilate has antioxidant effects and is frequently used as an anticoagulant during renal replacement therapy. We aimed to investigate the effect of nafamostat mesilate on plasma linezolid concentration. We examined whether the co‐administration of linezolid and nafamostat had any effect on plasma linezolid concentration. Mice were randomly allocated to two groups (n = 18/group): linezolid (100 mg kg−1, subcutaneous injection) + nafamostat (30 mg kg−1, intraperitoneal injection) and linezolid + saline. At 5 hours, the linezolid concentration was significantly higher in the linezolid + nafamostat co‐administration group than that in the linezolid + saline group (20.6 ± 9.8 vs 3.6 ± 1.2 μg/mL, respectivelyP< .001). The antioxidant effects of nafamostat may inhibit linezolid metabolism, resulting in the adverse event of high linezolid concentration if both are administered concurrently during renal replacement therapy.