中文摘要：

目的建立一种预测在治疗药物监测中需要避免的、只能提供很少信息的“最小信息采样点”的方法。方法进行了一系列基于一室开放模型的仿真，并且通过比较不同采样方案中预测参数效果的差异来验证建立的预测最小信息采样点的方法是否合理。我们比较了每种采样方案中各个参数的预测值和真实值（仿真值），通过两者的接近程度来评价该采样方案，预测值和真实值越接近说明通过该方案采样获得的信息量越大，这个采样方案越合理。结果在预测的最小信息采样点附近的时间点采样，将会得到准确度和精确度均不佳的参数预测值。此外，还考查了预测的最小信息采样点和参数之间的关系。计算了一些典型情况下的最小信息采样点，并通过作图，了解它们与参数之间的变化关系。在本文研究的例子中，清除率可预测出一个最小信息采样点而表观分布容积和吸收速率常数各有两个。并且还发现最小信息采样点的预测值随表观分布容积的增大或者清除率和吸收速率常数的减小而增大。结论在实际的治疗药物监测中，可以根据按照本文所描述的方法预测出的最小信息采样点设计更加合理的采样方案。

英文摘要：

Aim To develop a method to estimate population pharmacokinetic parameters with the limited sampling time points provided clinically during therapeutic drug monitoring. Methods Various simulations were attempted using a one-compartment open model with the first order absorption to determine PK parameter estimates with different sampling strategies as a validation of the method. The estimated parameters were further verified by comparing to the observed values. Results The samples collected at the single time point close to the non-informative sampling time point designed by this method led to bias and inaccurate parameter estimations. Furthermore, the relationship between the estimated non-informative sampling time points and the values of the parameter was examined. The non-informative sampling time points have been developed under some typical occasions and the results were plotted to show the tendency. As a result, one non-informative time point was demonstrated to be appropriate for clearance and two for both volume of distribution and constant of absorption in the present study. It was found that the estimates of the non-informative sampling time points developed in the method increase with increases of volume of distribution and the decrease of clearance and constant of absorption. Conclusion A rational sampling strategy during therapeutic drug monitoring can be established using the method present in the study.