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药物剂量个体化的假设。

Hypothesis for the individualisation of drug dosage.

作者信息

Koup J R, Sack C M, Smith A L, Gibaldi M

出版信息

Clin Pharmacokinet. 1979 Nov-Dec;4(6):460-9. doi: 10.2165/00003088-197904060-00005.

Abstract

Computer simulations based on the pharmacokinetics of chloramphenicol and theophylline in patients, indicate a very strong correlation (r = 0.988 for chloramphenicol and r = 0.971 for theophylline) between log maintenance dose required to achieve a desired average drug concentration in serum at steady-state, and the drug concentration in serum 6 hours after an initial test dose administered by constant rate intravenous infusion over 0.5h. Accordingly, we have developed a nomogram to predict individual daily dosing requirements for these drugs in uncomplicated patients from a single serum assay following an initial dose. Within defined limits, predictions made with the nomogram are essentially equivalent to those made by iraditional pharmacokinetic methods which require substantially more drug concentration-time data following a test dose. Predictions based on the nomogram are relatively unaffected by small but typical errors in magnitude of the test dose, infusion time, sampling time and assay. Protocols for the administration of the test dose other than described, e.g. administration of an oral theophylline solution, may be equally useful for dosage predictions. In principle, this approach should apply to other drugs.

摘要

基于氯霉素和茶碱在患者体内的药代动力学进行的计算机模拟表明,在稳态下达到血清中所需平均药物浓度所需的对数维持剂量,与在0.5小时内通过恒速静脉输注给予初始试验剂量6小时后血清中的药物浓度之间存在非常强的相关性(氯霉素的r = 0.988,茶碱的r = 0.971)。因此,我们制定了一张列线图,通过初始剂量后的单次血清检测来预测单纯患者中这些药物的个体每日给药需求。在规定的限度内,用列线图做出的预测与传统药代动力学方法做出的预测基本等效,而传统方法在试验剂量后需要更多的药物浓度 - 时间数据。基于列线图的预测相对不受试验剂量大小、输注时间、采样时间和检测中微小但典型误差的影响。除所述之外的试验剂量给药方案,例如口服茶碱溶液的给药,可能同样有助于剂量预测。原则上,这种方法应适用于其他药物。

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