Pokorná Pavla, Šíma Martin, Černá Olga, Allegaert Karel, Tibboel Dick, Slanař Ondřej
Department of Pediatrics - PICU/NICU, General University Hospital, 1st Faculty of Medicine Charles University in Prague , Prague , Czech Republic.
Department of Pharmacology, General University Hospital, 1st Faculty of Medicine Charles University in Prague , Czech Republic , Prague , Czech Republic.
J Chemother. 2019 Oct;31(6):307-312. doi: 10.1080/1120009X.2019.1599574. Epub 2019 Apr 14.
This study aimed to explore vancomycin pharmacokinetics and its covariates in critically ill neonates and to propose an easy applicable dosing nomogram for initial treatment. Individual vancomycin pharmacokinetic parameters were calculated based on therapeutic drug monitoring data using a one-compartmental model. A linear regression model was used for examination of covariates. The mean (SD) volume of distribution (Vd) and clearance (CL) for vancomycin were 0.73 (0.31) L/kg and 0.052 (0.020) L/h/kg, respectively. Vd was related to actual body weight (ABW), gestational and postmenstrual age. CL was also associated with ABW, gestational, postmenstrual age and also creatinine clearance. ABW was the strongest predictor for vancomycin pharmacokinetics and consequently dosing. Loading dose (mg) of 11.81 × ABW (kg) + 7.86 and maintenance dose (mg/day) of 40.92 × ABW (kg) -22.18 most closely approximated pharmacokinetic target. Vancomycin pharmacokinetics was mainly influenced by ABW in neonates and a practical ABW-based dosing algorithm was developed.
本研究旨在探讨危重新生儿万古霉素的药代动力学及其协变量,并提出一种易于应用的初始治疗给药剂量图。基于治疗药物监测数据,使用单室模型计算个体万古霉素药代动力学参数。采用线性回归模型检查协变量。万古霉素的平均(标准差)分布容积(Vd)和清除率(CL)分别为0.73(0.31)L/kg和0.052(0.020)L/h/kg。Vd与实际体重(ABW)、胎龄和月经后年龄有关。CL也与ABW、胎龄、月经后年龄以及肌酐清除率有关。ABW是万古霉素药代动力学及给药剂量的最强预测因子。11.81×ABW(kg)+7.86的负荷剂量(mg)和40.92×ABW(kg)-22.18的维持剂量(mg/天)最接近药代动力学目标。新生儿万古霉素药代动力学主要受ABW影响,并制定了基于ABW的实用给药算法。