【作者】 刘越；

【导师】 孙鹤； 魏静；

【作者基本信息】 天津大学 ， 药理学， 2012， 硕士

【摘要】 在临床试验中，药物的AUC测量一直采用传统传统方法即梯形法，进行估算。而当药物半衰期比较长的时候，传统的方法存在着局限性。首先是取血点密集程度和模拟值准确度的矛盾；其次是取血点如果太长对病人治疗时间要求长，入组病人条件苛刻。基于以上考虑，本文旨在探讨静脉给药一室模型的条件下，新的AUC值估算方式，力求找到新的采血方式，新的模拟模型进行计算。使得针对AUC的估算值与理想值偏差不超过15%。同时令采血点尽可能的减少和提前，这样一方面能够降低病人治疗时间从而降低病人的入组条件，另一方面，如果方法可行，可以使病人的痛苦降低。在这样的研究思路的指导下，本研究先制定了九种取血方案，然后制定新方法，接着基于九种方案进行新方法和常规方法估算AUC值得比对。最后，比较在不同的情况下，选择何种采血方法和模拟计算方式进行估算。总体来说，A值越小，则估算值的误差率越低，在实验可能的情况下，设计实验方案的时候应该尽量想前段取血。同时借用编程的手段，为1000次模拟实验进行程序上的保证。力求提高研究效率节约研究成本，最重要的是使得研究结果更为精确。最后我们选取了几组实验进行了生物等效性实验设计的验证，对估算结果进行生物等效性实验后，才可以说明实验方案是否奏效。更多还原

【Abstract】 The traditional methods to estimate AUC measurement in clinical trials in Chinawhich has been using is the trapezoidal method.However, the relatively long half-livesof drugs, traditional methods have their limitations. The first is the intensity andaccuracy of the analog value contradiction of the blood points; followed by bloodpoint is too long treatment time for patients requiring long into the group of patientsunder harsh conditions.Based on the above considerations, this paper aims to explore the conditions of theone-compartment model of intravenous administration, the AUC value estimationmethod, and strive to find new blood, new simulation model is calculated. Estimatesfor the AUC and the ideal deviation does not exceed15%. Another blood collectionpoint, at the same time, minimize and early, so that one can reduce patient treatmenttime thereby reducing the patient’s inclusion criteria, on the other hand, if feasible, canmake the suffering of the patients reduce.Under the guidance of this idea, this study first established the nine kinds of bloodprogram, and then develop a new method, then the new method and conventionalmethods to estimate the AUC is worth more than nine kinds of programs. Finally, tocompare the different circumstances, the choice of blood collection methods andsimulation calculation to estimate. In general, the smaller A value, the lower estimatedthe margin of error is in experiment. If possible, design the plan should try to choosethe front position for samplingMeans of borrowed programming, procedural guarantees for the1000simulation.Strive to improve the efficiency of research to save research costs, the most importantthing is to make research results more precise.Finally, we selected several groups of experimental bioequivalence validation of theexperimental design, bioequivalence experiment on the estimation results can explainthe experimental program are working.更多还原