药学学报, 2019, 54(3): 528-532
引用本文:
郭晴, 刘滔滔, 经力, 庞惠媚, 农光民, 唐双意, 陈峋. 中国儿童万古霉素群体药代动力学模型的外部验证与分析[J]. 药学学报, 2019, 54(3): 528-532.
GUO Qing, LIU Tao-tao, JING Li, PANG Hui-mei, NONG Guang-min, TANG Shuang-yi, CHEN Xun. Predictive performance and analysis of a vancomycin population pharmacokinetic model in Chinese pediatric patients[J]. Acta Pharmaceutica Sinica, 2019, 54(3): 528-532.

中国儿童万古霉素群体药代动力学模型的外部验证与分析
郭晴1, 刘滔滔1, 经力1, 庞惠媚1, 农光民2, 唐双意1, 陈峋2
1. 广西医科大学第一附属医院药学部, 广西 南宁 530021;
2. 广西医科大学第一附属医院儿科, 广西 南宁 530021
摘要:
本文旨在外部验证前期建立的0~10岁中国儿童万古霉素群体药动学(population pharmacokinetics,PPK)模型。本研究经广西医科大学第一附属医院伦理委员会批准,通过回顾性收集2013年8月至2017年5月期间在广西医科大学第一附属医院静脉应用万古霉素治疗的≤ 10岁的患者,根据前期建立的儿童万古霉素PPK模型,运用贝叶斯分析法求出给定剂量下的万古霉素浓度个体预测值,与实测值比较,评估模型的预测性能。结果共纳入191例患者371个血药浓度值。万古霉素个体预测值与实测值的平均预测误差(ME)、平均相对预测误差(ME%)、平均绝对误差(MAE)和均方根误差(RMSE)分别为-0.50 mg·L-1、6.03%、1.84 mg·L-1和2.86 mg·L-1;个体预测值与实测值的相关系数为0.95;相对预测误差在±30%以内的血药浓度值约占82.75%;拟合优度(goodness-of-fit)、直观预测检验法(VPC)和Bland-Altman一致性评价显示最终模型稳定,预测结果可靠。结果表明前期建立的0~10岁儿童万古霉素PPK模型具有较高的预测性能,可用于万古霉素初始治疗方案的制定和药物暴露程度的预测。
关键词:   
Predictive performance and analysis of a vancomycin population pharmacokinetic model in Chinese pediatric patients
GUO Qing1, LIU Tao-tao1, JING Li1, PANG Hui-mei1, NONG Guang-min2, TANG Shuang-yi1, CHEN Xun2
1. Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China;
2. Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
Abstract:
This study aimed to evaluate the predictive performance of a vancomycin population pharmacokinetic model in 0-10 year Chinese pediatric patients. This study was approved by the Ethics Research Committee of the First Affiliated Hospital of Guangxi Medical University, data from hospitalized children ≤ 10 years of age who receiving vancomycin were collected retrospectively. Individual predictive values (IPRED) were estimated by Bayesian Analysis based on a previous published population pharmacokinetic model, and compared with the observed steady state trough concentration. As results, a total of 371 vancomycin serum concentrations from 191 patients were taken for the external validation. The mean error (ME), the mean relative prediction error (ME%), the mean absolute error (MAE) and the root mean square error (RMSE) in individual prediction method for the total patients were -0.50 mg·L-1, 6.03%, 1.84 mg·L-1, 2.86 mg·L-1 respectively. The correlation coefficient between individual predictions and detection values was 0.95. The stability and the predictive performance of model were accepted by goodness-of-fit, visual predictive check (VPC) and Bland-Altman. The percentage of individual prediction error within ±30% was 82.75%. The above results suggest that, this Chinese pediatric population pharmacokinetic model in 0-10 years old has a good prediction performance. It can be applied to the design of initial treatment plan and predicting the extent of drug exposure.
Key words:   
收稿日期: 2018-09-17
DOI: 10.16438/j.0513-4870.2018-0853
基金项目: 国家自然科学基金资助项目(81760671).
通讯作者: 刘滔滔
Email: liutaotao@gxmu.edu.cn
相关功能
PDF(416KB) Free
打印本文
0
作者相关文章

参考文献:
[1] Blaskovich MAT, Hansford KA, Butler MS, et al. Developments in glycopeptide antibiotics[J]. ACS Infect Dis, 2018, 4:715-735.
[2] Steinmetz T, Eliakim-Raz N, Goldberg E, et al. Association of vancomycin serum concentrations with efficacy in patients with MRSA infections:a systematic review and meta-analysis[J]. Clin Microbiol Infect, 2015, 21:665-673.
[3] Rybak MJ, Lomaestro BM, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adults summary of consensus recommendations from the American society of health-system pharmacists, the infectious diseases society of America, and the society of infectious diseases pharmacists[J]. Pharmacotherapy, 2009, 29:1275-1279.
[4] Madigan T, Sieve RM, Graner KK, et al. The effect of age and weight on vancomycin serum trough concentrations in pediatric patients[J]. Pharmacotherapy, 2013, 33:1264-1272.
[5] Arfa P, Karimi A, Rafiei Tabatabaei S, et al. A prospective study to assess vancomycin serum concentrations in pediatric patients with current dosing guidelines[J]. Iran J Pharm Res, 2016, 15:341-346.
[6] Ye ZK, Chen YL, Chen K, et al. Therapeutic drug monitoring of vancomycin:a guideline of the division of therapeutic drug monitoring, Chinese pharmacological society[J]. J Antimicrob Chemother, 2016, 71:3020-3025.
[7] Han Z, Pettit NN, Landon EM, et al. Impact of pharmacy practice model expansion on pharmacokinetic services:optimization of vancomycin dosing and improved patient safety[J]. Hosp Pharm, 2017, 52:273-279.
[8] Zane NR, Reedy MD, Gastonguay MR, et al. A population pharmacokinetic analysis to study the effect of therapeutic hypothermia on vancomycin disposition in children resuscitated from cardiac arrest[J]. Pediatr Crit Care Med, 2017, 18:e290-e297.
[9] Le J, Capparelli EV, Wahid U, et al. Bayesian estimation of vancomycin pharmacokinetics in obese children:matched case-control study[J]. Clin Ther, 2015, 37:1340-1351.
[10] Stockmann C, Sherwin CM, Zobell JT, et al. Population pharmacokinetics of intermittent vancomycin in children with cystic fibrosis[J]. Pharmacotherapy, 2013, 33:1288-1296.
[11] Sheng XY, Chen CY, Ma LY, et al. Population pharmacokinetics of vancomycin in Chinese infants[J]. Int J Clin Pharmacol Ther, 2017, 55:558-566.
[12] Zhang H, Wang Y, Gao P, et al. Pharmacokinetic characteristics and clinical outcomes of vancomycin in young children with various degrees of renal function[J]. J Clin Pharmacol, 2016, 56:740-748.
[13] Song L, He CY, Yin NG, et al. A population pharmacokinetic model for individualised dosage regimens of vancomycin in Chinese neonates and young infants[J]. Oncotarget, 2017, 8:105211-105221.
[14] Liu TT, Deng CH, Cheng DH, et al. Population pharmacokinetics of vancomycin in Chinese pediatric patients[J]. Int J Clin Pharmacol Ther, 2017, 55:509-516.
[15] FDA US. Guidance for industry on population pharmacokinetics; availability. Food and Drug Administration, HHS. Notice[J]. Fed Regist, 1999, 64:6663-6664.
[16] Deng CH, Liu TT, Wu K, et al. Predictive performance of reported population pharmacokinetic models of vancomycin in Chinese adult patients[J]. J Clin Pharm Ther, 2013, 38:480-489.
[17] He XR, Liu ZH, Ji SM, et al. Population pharmacokinetics of vancomycin and prediction of pharmacodynamics in the Chinese people[J]. Acta Pharm Sin (药学学报), 2014, 49:1528-1535.
[18] Stockmann C, Hersh AL, Roberts JK, et al. Predictive performance of a vancomycin population pharmacokinetic model in neonates[J]. Infect Dis Ther, 2015, 4:187-198.
[19] Marsot A, Vialet R, Boulamery A, et al. Vancomycin:predictive performance of a population pharmacokinetic model and optimal dose in neonates and young infants[J]. Clin Pharmacol Drug Dev, 2012, 1:144-151.
[20] Patel S, Bernice F. Vancomycin[M/OL]. StatPearls Publishing LLC. 2018[2018-11-11]. https://www.ncbi.nlm.nih.gov/books/NBK459263/.
[21] Le J, Ny P, Capparelli E, et al. Pharmacodynamic characteristics of nephrotoxicity associated with vancomycin use in children[J]. J Pediatric Infect Dis Soc, 2015, 4:e109-e116.
[22] Mehrotra N, Tang L, Phelps SJ, et al. Evaluation of vancomycin dosing regimens in preterm and term neonates using Monte Carlo simulations[J]. Pharmacotherapy, 2012, 32:408-419.
[23] de Hoog M, Mouton JW,van den Anker JN. Vancomycin:pharmacokinetics and administration regimens in neonates[J]. Clin Pharmacokinet, 2004, 43:417-440.
[24] Kato H, Hagihara M, Nishiyama N, et al. Assessment of optimal initial dosing regimen with vancomycin pharmacokinetics model in very low birth weight neonates[J]. J Infect Chemother, 2017, 23:154-160.
[25] Kearns GL, Abdel-Rahman SM, Alander SW, et al. Developmental pharmacology——drug disposition, action, and therapy in infants and children[J]. N Engl J Med, 2003, 349:1157-1167.
[26] Gao YC, Jiao Z, Huang H, et al. Development of decision system for individualization of vancomycin dosage[J]. Acta Pharm Sin (药学学报), 2018, 53:104-110.