Population pharmacokinetic and pharmacodynamic model of norvancomycin
会议名称：《中国药理学会临床药理学专业委员会会议暨第十次全国临床药理学学术会议》
会议日期：2007年
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
关 键 词：norvancomycin population pharmacokinetics nonlinear mixed effect model pharmacodynamics therapeutic drug monitoring fluorescence polarization immunoassay
摘 要：AIM:To evaluate the population pharmcokinetics(PPK) and pharmacodynamics(PD)of norvancomycin in patients. METHODS:We enrolled 146 patients who were con- firmed or suspected with gram-positive bacterial infections in this study.A PPK model was developed and validated by the analysis of NONMEM *** PK/PD profiles from the pharmacokinetic parameters in the patients and from MIC values were *** optimal dose regime was calculated by the analyses of the PK/PD model ac- cording to the clinical outcomes and bacterial *** norvancomycin MICs of clinically isolated swains from the patients population were determined by agar dilution meth- ods. RESULTS:The best model was a two compartment phar- macokinetic model with exponential interindividual error and additive residual error statistical *** finding of the study indicated that the change in Ccr values had impacts on drug clearance(CL).For example,CL of pa- tients with decreased renal function would be influenced. The increased volume of a peripheral distribution(V) was observed when norvancomycin was co-administered with *** logistic stepwise analyses revealed that ratio of AUC/MIC is a major factor which could signifi- candy determine the clinical outcomes and bacterial eradi- cation for patients. When the ratio of AUC/MIC was more than 579.90 for Staphylococcus aureus infections or it was more than 637.67 for Enterococal infections,approximately 95% of patients could achieve cure clinical outcome. CONCLUSION:AUC/MIC should be a major PK/ PD parameter to determine efficacy of *** optimized regimen of norvancomycin can be simulated and developed for different subgroups of bacterial infected pa- tients with special physiologic and pathologic features.