Evaluation of the Prediction Performance of Population Pharmacokinetic Models of Sodium Valproate in Epileptic Children in China
ZHAO Si-miao1,2, JIANG De-chun1,3, WANG Ya-wei1,3, LI Xiao-ling1,3*
1. Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing 100053, China; 2. School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China; 3. National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
Abstract：OBJECTIVE To compare all published sodium valproate population pharmacokinetic models of epileptic children in China and assess them by external validation to determine their predictive performance. METHODS The published population pharmacokinetic model of sodium valproate in children with epilepsy in China was collected by database retrieval. By retrospectively collecting patients' information, we performed an external validation to evaluate the power of prediction. RESULTS Four sodium valproate models were published before. The external validation of 101 samples showed that the MPE, MAE, RMSE of the four model were similar. All of them showed good adequacy between predicted concentrations and observed concentrations. Comparing with other models, the model established by Ding has better prediction error coincidence rate in most interval, which is more targeted for the prediction of individualized dosage regimen for epileptic children in our hospital. However, the overall prediction accuracy of the four models is not significantly different. CONCLUSION By the evaluation of four published population pharmacokinetic models of sodium valproate model B performs better than others, while the overall accuracy of the four models did not differ much. Racial difference may be an important factor affecting the accuracy of the model, which needs to be further explored in subsequent studies.
赵思邈, 姜德春, 王雅葳, 李晓玲. 中国癫痫儿童丙戊酸钠群体药动学模型预测性能评估[J]. 中国药学杂志, 2020, 55(3): 233-238.
ZHAO Si-miao, JIANG De-chun, WANG Ya-wei, LI Xiao-ling. Evaluation of the Prediction Performance of Population Pharmacokinetic Models of Sodium Valproate in Epileptic Children in China. Chinese Pharmaceutical Journal, 2020, 55(3): 233-238.
NEVALAINEN O P, ANSAKORPI H, AUVINEN A. Epilepsy-related clinical characteristics and mortality: a systematic review and Meta-analysis[J]. Neurology, 2015, 84(17):1823-1824.
[2]
DING J, WANG Y, LIN W, et al. A population pharmacokinetic model of valproic acid in pediatric patients with epilepsy: a non-linear pharmacokinetic model based on protein-binding saturation[J]. Clin Pharmacokinet, 2015, 54(3):305-317.
[3]
NEUROLOGY GROUP OF PEDIATRIC BRANCH OF CHINESE MEDICAL ASSOCIATION.Expert consensus on long-term management of epilepsy in children[J]. Chin J Pediatr(中华儿科杂志), 2013, 51(9):669-703.
[4]
BONDAREVA I B, JELLIFFE R W, ANDREEVA O V, et al. Predictability of individualized dosage regimens of carbamazepine and valproate mono- and combination therapy[J]. J Clin Pharm Ther, 2011, 36(5):625-636.
[5]
TAUZIN M, TRELUYER J M, NABBOUT R, et al. Simulations of valproate doses based on an external evaluation of pediatric population pharmacokinetic models[J]. J Clin Pharmacol, 2019, 59(3):406-417.
[6]
SERRANO B B, GARCIA S M, OTERO M J, et al. Valproate population pharmacokinetics in children[J]. J Clin Pharm Ther, 1999, 24(1):73-80.
[7]
SHEINER L B, BEAL S L. Some suggestions for measuring predictive performance[J]. J Pharmacol Biopharm, 1981, 9(4):503-512.
[8]
JIANG D C, WANG L, WANG Y Q, et al. Population pharmacokinetics of valproate in Chinese children with epilepsy[J]. Acta Pharmacol Sin(中国药理学报), 2007, 28(10):1677-1684.
[9]
JIANG D C, WANG L, LU W. Population pharmacokinetics of valproate in children with epilepsy by NONMEM[J]. Chin Pharm J(中国药学杂志), 2007, 42(4):291-294, 317.
[10]
ZHANG Z B, WU Y, JI S M, et al. Establishment of population pharmacokinetic models with valproic acid in different age groups of Chinese epileptic children[J]. Chin J Appl Clin Pcdiatr(中华实用儿科临床杂志), 2014, 29(9):698-703.
[11]
LAI J, LI X Q, WU L L, et al. Establishment of the individualized drug delivery flow path of vancomycin and case analysis[J]. Chin Hosp Pharm J(中国医院药学杂志), 2018, 38(15):1656-1660.
[12]
YANG S H, ZHANG Z B, LIU M, et al. A randomized controlled trial of initial valproic acid dosage in epileptic children[J]. Chin J Appl Clin Pediatr(中华实用儿科临床杂志), 2018, 33(12):905-908.
[13]
DORE M, SAN J A, FRENETTE A J, et al. Clinical importance of monitoring unbound valproic acid concentration in patients with hypoalbuminemia[J]. Pharmacotherapy, 2017, 37(8):900-907.
[14]
WALLENBURG E, KLOK B, DE JONG K, et al. Monitoring protein-unbound valproic acid serum concentrations in clinical practice[J]. Ther Drug Monit, 2017, 39(3):269-272.
[15]
O'HARA K. Paediatric pharmacokinetics and drug doses[J]. Aust Prescr, 2016, 39(6):208-210.
[16]
MACCHI-ANDANSON M, CHARPIAT B, JELLIFFE R W, et al. Failure of traditional trough levels to predict tacrolimus concentrations[J]. Ther Drug Monit, 2001, 23(2):129-133.
[17]
JIANG D C, WANG L. Population pharmacokinetic model of valproate and prediction of valproate serum concentrations in children with epilepsy[J]. Acta Pharmacol Sin(中国药理学报), 2004, 25(12):1576-1583.
[18]
HE J, YANG W H. Establishment of the individualized drug delivery model of vancomycin for infected patients based on population pharmacokinetics and its clinical application[J]. Chin J Clin Pharm (中国临床药学杂志), 2015, 24(1):27-31.
[19]
SHERWIN C M, KIANG T K, SPIGARELLI M G, et al. Fundamentals of population pharmacokinetic modelling: validation methods[J]. Clin Pharmacokinet, 2012, 51(9):573-590.
[20]
LIU Y O, CHEN C Y, SHENG X Y, et al. Validation of vancomycin population pharmacokinetic model for pediatric patients[J]. Chin Pharm J(中国药学杂志), 2016, 51(14):1245-1251.
[21]
ZHANG Z B, JI S M, HAN Y, et al. Population pharmacokinetic models of lamotrigine in different age groups of Chinese children with epilepsy[J]. Eur J Clin Pharmacol, 2017, 73(4):445-453.
[22]
VAN DIJKMAN S C, DE JAGER N, RAUWE W M, et al. Effect of age-related factors on the pharmacokinetics of lamotrigine and potential implications for maintenance dose optimisation in future clinical trials[J]. Clin Pharmacokinet, 2018, 57(8):1039-1053.
[23]
DE COCK R F, PIANA C, KREKELS E H, et al. The role of population PK-PD modelling in paediatric clinical research[J]. Eur J Clin Pharmacol, 2011, 67(1):5-16.
[24]
CHARLES B. Population pharmacokinetics: an overview[J]. Australian Prescriber, 2014, 37(6):210-213.
2020, Vol. 55 
