血药浓度监测下大剂量甲氨蝶呤24h滴注疗法延迟排泄分析

目的:研究非霍奇金淋巴瘤患者大剂量甲氨蝶呤(HD-MTX)24 h滴注疗法延迟排泄影响因素、不良反应和解救措施。方法:收集某院2009-2014年之间122个患者的377次疗程的HD-MTX 24 h滴注疗法的资料,运用统计学方法分析延迟排泄和疗程、年龄、性别、剂量、血药浓度及不良反应的相关关系,探讨了延迟排泄的解救措施。结果:延迟排泄发生率与疗程、年龄、性别无关,但与剂量相关,当剂量大于4.0 g时发生率高。延迟排泄患者滴注完12 h以后的MTX血药浓度明显升高,高浓度MTX延迟排泄的可引起肾功能损伤。结论:延迟排泄更多发生在低浓度点,但高浓度的延迟排泄肾功能损伤大,因此血药浓度监测是实施HD-MTX疗法必不可少的安全保证措施。在及时的亚叶酸钙(CF)解救和充分的水化碱化下,延迟排泄的不良反应完全可以很好地预防和控制。

Analysis of excretion delay of 24 hour high dose methotrexate by therapeutic drug monitoring

OBJECTIVE To study causal factors, toxic and side effects, rescue of excretion delay of 24 h high dose methotrexate in patients with non Hodgkin lymphoma by using therapeutic drug monitoring (TDM).METHODS Data of 122 patients and 377 treatment courses of HD-MTX from 2009 to 2014 were collected. Correlation of treatment course, age, gender, dose, plasma concentration and side effects with excretion delay were analyzed by statistical method, and measures of rescue were discussed. RESULTS Treatment course, age and gender were independent factors for excretion delay. Excretion delay raised when dose was greater than 4.0 g. Plasma concentration of MTX after 12 h was higher in patients experiencing excretion delay. Renal damage occurred in patients experiencing excretion delay with high MTX plasma concentration.CONCLUSION Excretion delay occurs more frequently at low MTX concentrations, but excretion delay at high MTX concentrations may cause serious renal damage, so TDM is necessary and essential to HD-MTX. Toxic and side effects are under control by timely rescue of CF with sufficient hydration and alkalization.