CAJ | 학술논문

目的：验证通过非线性混合效应模型法（NONM EM ）软件建立的万古霉素群体药动学模型在神经外科重症患者中应用的有效性和实用性。方法回顾性收集2013年3月—2014年3月南京鼓楼医院神经外科重症加护病房中给予万古霉素治疗患者的性别、年龄、体重、血肌酐和血白蛋白数值，通过前期建立的群体药动学模型，计算特定给药剂量下万古霉素的稳态血药谷浓度预测值，并与实际测量值比较，进而统计学分析验证。结果共收集患者42例，测得万古霉素血药谷浓度53份，平均谷浓度为10．9mg／L，范围为1．6～49．1mg／L。群体药动学模型的预测值与实际测量值有显著相关性（r＝0．857， P＜0．001），平均绝对百分比误差（MAPE）为0．4079，预测值的95％置信区间为9．36～14．07，实测值的95％置信区间为8．92～14．32。结论该群体药动学模型可以用于神经外科重症患者给予万古霉素前的预测和药物剂量的指导。但由于神经外科危重症患者昏迷，体重估计误差较大（约30％），同时对比剂和利尿药导致的肾功能改变影响结果。通过调整使用方法，预测准确率提高到近70％。
목적：험증통과비선성혼합효응모형법（NONM EM ）연건건립적만고매소군체약동학모형재신경외과중증환자중응용적유효성화실용성。방법회고성수집2013년3월—2014년3월남경고루의원신경외과중증가호병방중급여만고매소치료환자적성별、년령、체중、혈기항화혈백단백수치，통과전기건립적군체약동학모형，계산특정급약제량하만고매소적은태혈약곡농도예측치，병여실제측량치비교，진이통계학분석험증。결과공수집환자42례，측득만고매소혈약곡농도53빈，평균곡농도위10．9mg／L，범위위1．6～49．1mg／L。군체약동학모형적예측치여실제측량치유현저상관성（r＝0．857， P＜0．001），평균절대백분비오차（MAPE）위0．4079，예측치적95％치신구간위9．36～14．07，실측치적95％치신구간위8．92～14．32。결론해군체약동학모형가이용우신경외과중증환자급여만고매소전적예측화약물제량적지도。단유우신경외과위중증환자혼미，체중고계오차교대（약30％），동시대비제화이뇨약도치적신공능개변영향결과。통과조정사용방법，예측준학솔제고도근70％。
Objective This study was designed to validate the utility of a population pharmacokinetic model established for vancomycin in patients with severe neurosurgical disease . Methods The clinical data including patient gender , age , body weight ,serum creatinine and albumin were collected retrospectively from patients in Nanjing Drum Tower Hospital to calculate the steady trough concentration of vancomycin using the previously established pharmacokinetic model .The predicted value was compared with the actual value .Results During the period from March 2013 to March 2014 ,53 blood samples with serum trough concentration of vancomycin were collected from 42 patients .The average trough concentration of vancomycin was 10 .9 mg/L (range from 1 .6 to 49 .1 mg/L) .The predicted trough level of vancomycin based on the population pharmacokinetic model was significantly correlated to the actual value(r=0 .857 ,P<0 .001) .The mean absolute percentage error was 0 .407 9 . The confidence interval was 9 .36‐14 .07 for the predicted values ,and 8 .92‐14 .32 for the actual values .Conclusions The pharmacokinetic model is valid and useful for planning intravenous dose of vancomycin in patients with severe neurosurgical disease .Large error (about 30% ) was observed in estimation of body weight due to coma .Reduced renal function following contrast agent and/or diuretic drug has an impact on the predicted results . The accuracy of prediction can be increased to nearly 70% after adjusting the covariates .