基于群体药动学原理对1例甲氨蝶呤严重排泄延迟患儿的药学监护
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篇名: 基于群体药动学原理对1例甲氨蝶呤严重排泄延迟患儿的药学监护
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摘要: 目的:探讨群体药动学(PPK)在甲氨蝶呤(MTX)严重排泄延迟急性淋巴细胞白血病(ALL)患儿个体化解救过程中的价值,为临床药学服务提供参考。方法:临床药师参与1例MTX严重排泄延迟ALL患儿的临床解救过程。患儿接受大剂量MTX(HD-MTX)化疗后,出现MTX严重排泄延迟。临床药师借助PPK模型和贝叶斯反馈法预测患儿体内MTX血药浓度,并根据实测及预测结果在亚叶酸钙(CF)初始解救剂量(15 mg/m2,ivgtt,q6 h)的基础上,将入院第6、7天的CF解救剂量调整至160 mg/次,维持静脉滴注1 h;入院第8天,调整至42 mg/次;入院第9、10天,调整至21 mg/次;入院第11~16天,调整至10.5 mg/次;均为每天给药4次。考虑到患儿肾功能轻度受损,临床药师建议停用奥美拉唑,改用西咪替丁注射液0.2 g,ivgtt,qd护胃,并将注射用头孢他啶减量至0.4 g,ivgtt,tid;并嘱临床加强水化、碱化及口腔黏膜护理。结果:医师采纳临床药师建议。患儿体内MTX血药浓度预测值与实测值的差值不超过±0.32 μmol/L,预测准确度良好。患儿在PPK模型指导下调整CF解救方案后,其体内MTX血药浓度降至0.13 μmol/L,顺利完成此次化疗,于入院第18天出院。结论:PPK理论可为MTX严重排泄延迟ALL患者的临床解救提供参考,可作为临床药师开展药学服务的切入点之一。当患者出现MTX严重排泄延迟时,临床药师应充分掌握影响MTX排泄的因素,从患者的生理、病理情况,联合用药,体内血药浓度等多方面综合考虑,以确保解救的及时、有效。
ABSTRACT: OBJECTIVE:To investigate the value of population pharmacokinetics (PPK) in individualized rescue for an acute lymphoblastic leukemia (ALL) child with severe methotrexate (MTX) excretion delay, and to provide reference for clinical pharmaceutical care. METHODS: Clinical pharmacists participated in clinical rescue for an ALL child with severe MTX excretion delay. The child suffered from severe MTX excretion delay after high dose MTX (HD-MTX) chemotherapy. Clinical pharmacists used PPK model and Bayesian feedback method to predict plasma concentration of MTX. According to measured results and predicted results, rescue dose of calcium folinate (CF) was adjusted to 160 mg/time on the 6th, 7th day after admission for intravenous dripping 1 h, based on initial rescue dose (15 mg/m2,ivgtt,q6 h) of CF; on the 8th day, CF rescue dose was adjusted to 42 mg/time; on the 9th, 10th day, CF rescue dose was adjusted to 21 mg/time; on the 11th-16th day, CF recue dose was adjusted to 10.5 mg/time; 4 times a day. Considering the mild impairment of renal function, clinical pharmacists proposed to discontinue omeprazole and use Cimetidine injection 0.2 g, ivgtt, qd, for protecting stomach, and decrease the dose of Cefazidime for injection to 0.4 g, ivgtt, tid; strengthen hydration, alkalization and oral mucosa care. RESULTS: Physicians adopted to the suggestions of clinical pharmacists. The difference between predicted value of plasma concentration of MTX and measured value was less than ±0.32 μmol/L. The predictive results showed favorable accuracy. After the adjustment of CF rescue plan under the guidance of PPK model, plasma concentration of MTX decreased to 0.13 μmol/L. The child completed chemotherapy successfully and discharged from the hospital on the 18th day after admission. CONCLUSIONS: PPK theory can provide reference for clinical rescue in ALL patients with severe MTX excretion delay, and can be used as one of breakthrough points for clinical pharmacists to carry out pharmaceutical care. When the patient suffered from severe MTX excretion delay, clinical pharmacists should fully grasp the influential factors of MTX excretion, and consider the physiological and pathological conditions of the patients, drug combination and plasma concentration, so as to ensure the timely and effective rescue.
期刊: 2018年第29卷第4期
作者: 李思婵,徐华,汪洋
AUTHORS: LI Sichan,XU Hua,WANG Yang
关键字: 甲氨蝶呤;亚叶酸钙;排泄延迟;解救;群体药动学;贝叶斯反馈法;药学监护
KEYWORDS: Methotrexate; Calcium folinate; Excretion delay; Rescue; Population pharmacokinetics; Bayesian feedback method; Pharmaceutical care
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