Forecasting individual pharmacokinetics
Forecasting individual pharmacokinetics
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DOI：
10.1002/cpt1979263294
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发表时间：
1979-09
影响因子：
6.7
通讯作者：
L. Sheiner;S. Beal;B. Rosenberg;Vinay V. Marathe
中科院分区：
文献类型：
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作者：
L. Sheiner;S. Beal;B. Rosenberg;Vinay V. Marathe
通常可以用血浆浓度（CP）作为“治疗”终点来合理选择药物剂量。准确预测由剂量方案引起的CP的能力是选择该方案的核心。传统上，预测只能通过考虑已知的药代动力学影响因素，如性别、年龄和肾脏疾病来尝试。还必须对以前观察到的cp进行调整。在这里，我们讨论并解释了这两个任务的方法，主要集中在后者。考虑到观察CP误差，该方法平衡了观察结果与先前预期。对于地高辛，使用1个测量的CP，而不是不使用，将未来CP的预测精度提高了40%（预测误差方差的减少），2个CPs将其提高了67%。随着使用的CPs数量的增加，预测精度也会增加（预测误差平均值的减少）。仅在2之后，预测的准确度和精度就达到了理论上可能的水平。此外，来自CPs的信息远比来自可观察到的患者特征（性别、年龄等）的信息更有价值；使用所有后一种信息并不能像只使用1 CP那样提高准确度和精密度。
Often drug dosage may be chosen rationally by use of plasma concentration (CP) as the “therapeutic” end point. The ability to accurately forecast the CP resulting from a dosage regimen is central to choosing that regimen. Traditionally forecasting has been attempted only by accounting for known influences on pharmacokinetics, such as sex, age, and renal disease. One must also adjust for previously observed CPs. Herein, we discuss and explain an approach to both of these tasks, mainly focusing on the latter. The approach balances observed outcomes against prior expectations taking account of observation CP error. For digoxin, use of 1 measured CP, as opposed to none, improves forecast precision for future CPs by 40% (decrement in variance of forecast error), and 2 CPs improve it by 67%. There is also an increase in forecast accuracy (decrement in mean of forecast error) as the number of CPs used increases. After only 2, forecast accuracy and precision are as good as theoretically possible. Moreover, information from CPs is far more valuable for forecasting than that from observable patient features—sex, age, and the like; use of all the latter information does not improve accuracy and precision as much as only 1 CP.