地高辛临床药物动力学参数的预测及个体化给药方案

用Bayesian一点法拟合心衰病人的DG个体药物动力学参数及个体化给药方案,用minitab对软件DG群体药物动力学数据进行统计学分析.以CrCL为固定效应变量,建立系列回归模型,预测心衰病人的DG个体药物动力学参数、个体化给药方案及其对映的(?)ss.结果显示CrCL与DG群体药物动力学参数存在高度的相关(P<0.001),相关系数分别为:CL=0.805,Vd=0.985,T_(1/2)=-0.517,K=0.525,D_(1.0)=0.714.并建立定量回归模型,预测DG个体药物动力学参数,预测参数与实测参数没有统计学差异,其中以Vd预测精度最好,有95%的预测值在实测值的95%置信限以内.与实测值相关系数为0.974,估计标准误差小于3.3%;其次是CL,有2/3的预测值在实测值95%置信限以内,与实测值相关系数为0.797,估计标准误差小于20%;T_(1/2)和K预测结果稍差.CrCL预测的个体化给药方案80%符合最佳个体化给药方案,且两者所对应的(?)ss没有显著性差异.

THE PREDICTION OF DIGOXIN CLINICAL PHARMACOKINETIC PARAMETERS AND EVALUATION OF INDIVIDUAL DOSAGE REGIMENS

Using the method of one point of Bayesian individual pharmacokinetic parameters and dosage regimens of digoxin were calculated in heart failure patients,and the population pharmacokinetic data analysed in statistics with a minitab software. While CrCL being steady-reaction variable,the series of regression models were suggested and the individual pharmacokinetic parameters of digoxin in heart failure patients,individual dosage regimen as well as the corresponding average steady state serum concencration (Css) were predicted. The results showed that there were strong correlations (P<0. 001) between CrCL and the population pharmacokinetic parameters of digoxin,and the correlation coefficients were CL = 0. 805,Vd=0. 985,Tl/2 = 0. 517,K = 0. 525,D1.0=0. 714 respectively. The individual pharmacokinetic parameters of digoxin predicted by the founding of quantity regression models were not significant different to the "observed" parameters . Among those predicted parameters, Vd was the most precise one that 95% predicted value was in the 95% confidence limits for "observed" value with the correlation coefficient between predicted Vd value and the "observed" value being 0.974, the estimated standard error (SE) was less than 3. 3%; The predicted CL that 2/3 predicted value were in the 95% confidence limits for the "observed" value was less precise with the correlation coefficient being 0. 797 and the SE less than 20%; The predicted T1/2 and K were a little bad. 80% dosage regiments that were predicted according to CrCL corresponds with the best individual dosage regiments and the corresponding Css of either wasn't significent difference.