药代动力学非房室模型终末段半衰期的算法研究

目的:评价非房室模型终末段半衰期(t1/2z)不同计算方法的准确度和精密度,为t1/2z算法优选提供依据.方法:在不同个体间变异(CV,CV＝15％,25％,35％)下,用静注二室房室模型参数进行数据模拟,分别获得1000个受试者完整时间与浓度(C-T)曲线数据,再按样本量(N,N=15,25,35,45)用Bootstrap方法抽样1000次,最后获得12个数据集,用4种方法(5点法,4点法,6点法,全点法)计算每个数据集消除相不同点时的t1/2z,其结果的均值与真值(静注二室模型的消除半衰期)比较作为准确度,其标准差大小作为稳定性.结果:当C-T曲线消除相有4个点时,5点法计算值最准确且较为稳定,而6点法最为稳定;当消除相3点时,4点法计算值准确度最高且较为稳定,而6点法最为稳定;消除相2点时,4种方法准确度稳定性皆低.结论:消除相有效浓度点应至少3点,5点法和4点法计算t1/2z较为合理.

Study of the algorithm of elimination half-life time in pharmacokinet- ics

AIM： To study a reasonable algo- rithm of terminal half-life time （t1/2z） in pharma-cokinetics by the accuracy and precision. METH- ODS. The plasma concentration-time data of pu-erarin was simulated for 1000 subjects by using parameters of intravenous two-compartment models in the variations of 15%, 25% and 35%. Resampling 15, 25, 35, and 45 from the 1000 subjects were used to calculate t1/2, by 4-point, 5-point, 6-point, all-point methods when there were different points in eliminate phase. The re- suits of these methods were compared to the true value and expressed by accuracy and precision. RESULTS：The 5-point method can provide a t1/2z with better accuracy and precision when there are four concentration points in eliminate phase, the 4-point method provide the one with betteraccuracy in three points in eliminate phase, 6- point method provide t1/2z with better precision in both three and four points in eliminate phase. There is no reasonable t1/2z in all four methods if there are two points in eliminate phase. CON- CLUSION. Three concentration points should be at least included in eliminating phase for calcu- lating a t1/2z which is usually more reasonable in 4-points or 5-points method.