Pharmacokinetics of high-dose methotrexate with citrovorum factor rescue.
Pharmacokinetics of high-dose methotrexate with citrovorum factor rescue.
复制标题
大剂量甲氨蝶呤与柠檬酸因子救援的药代动力学。
DOI：
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发表时间：
1977
期刊：
影响因子：
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通讯作者：
Thomas L. Lincoln
中科院分区：
文献类型：
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作者：
W. Isacoff;Morrison Pf;Jerry Aroesty;K. Willis;Block Jb;Thomas L. Lincoln
在开始输注后72小时内，对172例大剂量输液的甲氨蝶呤(MTX)血药浓度进行了测定。药代动力学分析表明，双指数函数可以很好地描述所有剂量下的血浆衰变。在给定剂量下，血浆清除量在患者群体中的分布具有双指数清除量函数和相关的随时间变化的特征。结果发现，当每个等离子体清除函数按其各自的剂量进行刻度时，所产生的单位剂量曲线的1SD谱带在其整个时间范围内重叠，因此彼此之间没有显著差异。因此，50-200 mg/kg范围内的血浆清除量可用一个半衰期为1.8+/-0.1和8.4+/-0.5小时的单剂量可扩展双指数模型来表示。对于给定的最大允许血浆MTX水平(例如，24小时的10(-5)M)，清除量分布的变化可以预测需要加强抢救的患者的预期比例。在50-300 mg/kg的剂量范围内，尿清除量为104+/-8毫升/分钟，72小时后只有60%的甲氨蝶呤从尿液中排出。
The methotrexate (MTX)-plasma concentrations of 172 high-dose infusions over the range of 50-200 mg/kg were measured over the 72-hour period following the beginning of infusion. Pharmacokinetic analysis shows that a biexponential function adequately describes the plasma decay for all doses. The distribution of plasma clearances over the patient population at a given dose has been characterized by a biexponential clearance function and associated time-dependent variance. It is found that when each of the plasma clearance functions are scaled by their respective dose, the 1 SD bands about the resulting unit dose curves overlap throughout their time ranges and are therefore insignificantly different from one another. Thus, the plasma clearance over the 50-200-mg/kg range may be represented by a single dose-scalable biexponential model with half-lives of 1.8 +/- 0.1 and 8.4 +/- 0.5 hours. For a given maximum allowable plasma-MTX level (eg, 10(-5) M at 24 hours), the variance of the clearance distribution is shown to predict the expected fraction of patients who will require intensified rescue. Urinary clearance has been determined at 104 +/- 8 ml/minute over the dose range of 50-300 mg/kg and only 60% of the MTX was excreted in the urine by 72 hours.