DOSAGE REGIMEN BASED ON A SMALL AMOUNT OF DATA

基于少量数据的剂量方案

• 批准号: 63571090
• 负责人: RIKIHISA Tadaaki
• 金额: $ 1.22万
• 依托单位: CHIBA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63571090/
• 关键词: Small amount of data; Single point method; Bayesian method; Blood drug concentration; Steady-state concentration; Lithium; Amitriptyline; High pressure liquid chromatography; 少数データ; 高速液体クロマトグラフィー

Pharmacokinetics is useful for individualizing drug therapy. But frequent measurements of blood drug concentrations are usually difficult in a routine clinical practice. Therefore there is a need for a simple method which provides adequate prediction of drug concentrations from a small amount of data.Single point method and Bayesian method attracted our attention. The present study was undertaken to investigate the utility and the limit of these two method by using lithium carbonate and amitriptyline hydrochloride.Minimum steady-state concentrations of serum lithium at 1 week after initiation of therapy could be predicted within 20% error by single point method. This result was almost identical to that of Bayesian method. In 3 cases, the reduction of lithium clearance was observed at 1 to 6 months after initiation of therapy. In these case prediction of concentration was not good.Concentrations of amitriptyline in plasma were measured by an improved high pressure liquid chromatography. Mean error of amitriptyline prediction for 3 weeks was about 20% by both method but the variance was greater than lithium. Population parameters were obtained from our 8 patients and plasma amitriptyline concentrations were predicted in 3 patients for a longer period. Mean error was about 25%.It can be concluded that the single point method is simple and useful in predicting drug concentrations especially in few weeks and that the Bayesian method is reliable although the calculation is not simple.

药代动力学对于个体化药物治疗很有用。但在常规临床实践中，频繁测量血液药物浓度通常很困难。因此，需要一种简单的方法，能够从少量数据中充分预测药物浓度。单点方法和贝叶斯方法引起了我们的注意。本研究通过使用碳酸锂和盐酸阿米替林来探讨这两种方法的实用性和局限性。通过单点法可以预测治疗开始后1周时血清锂的最低稳态浓度，误差在20%以内。这个结果与贝叶斯方法的结果几乎相同。在 3 例病例中，在开始治疗后 1 至 6 个月观察到锂清除率降低。在这些情况下，浓度预测不好。通过改进的高压液相色谱法测量血浆中阿米替林的浓度。两种方法预测阿米替林 3 周的平均误差约为 20%，但方差大于锂盐。我们从 8 名患者中获得了群体参数，并对 3 名患者的血浆阿米替林浓度进行了较长时间的预测。平均误差约为25%。可以得出结论，单点法简单且适用于预测药物浓度，特别是几周内的药物浓度，贝叶斯方法虽然计算不简单，但可靠。