Methaneethorn Janthima
Pharmacokinetic Research Unit, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, and Center of Excellence for Environmental Health and Toxicology, Naresuan University, Phitsanulok, Thailand.
Clin Ther. 2017 Jun;39(6):1171-1181. doi: 10.1016/j.clinthera.2017.04.005. Epub 2017 May 5.
This study characterized the population pharmacokinetic properties of valproic acid in patients with mania and determined potential factors that affect the pharmacokinetic properties of valproic acid in this population.
Routine therapeutic drug monitoring of valproic acid concentrations, demographic data, and concomitant medications from 206 hospitalized patients with mania were retrospectively collected from Somdet Chaopraya Institute of Psychiatry and Srithanya Hospital, Thailand. Nonlinear mixed-effect modeling was used for data analysis. Covariate model building was conducted using stepwise forward addition and stepwise backward elimination. The final model was evaluated using bootstrap analysis and normalized prediction distribution error. The results were compared with those previously reported in patients with epilepsy given that there is an evidence of a difference in valproic acid clearance between patients with mania and those with epilepsy.
Valproic acid data were adequately described by a 1-compartment model. Significant predictors for valproic acid clearance included valproic acid dose and weight. The population estimates for valproic acid CL/F and V/F were 0.464 L/h and 23.3 L, respectively. Valproic acid clearance obtained from this study did not seem to be significantly different from that of patients with epilepsy.
A qualified population pharmacokinetic model for valproic acid in patients with mania was developed. This model could be used to optimize valproic acid therapy in patients with mania. Valproic acid clearance could be predicted from valproic acid dose and weight of patients. This predicted clearance can subsequently be used for individualization of optimum valproic acid maintenance dose.
本研究对躁狂症患者丙戊酸的群体药代动力学特性进行了表征，并确定了影响该群体丙戊酸药代动力学特性的潜在因素。
回顾性收集了泰国诗丽通公主精神病学研究所和斯里塔尼亚医院206例住院躁狂症患者的丙戊酸浓度常规治疗药物监测数据、人口统计学数据及合并用药情况。采用非线性混合效应模型进行数据分析。协变量模型构建采用逐步向前加入法和逐步向后剔除法。使用自抽样分析和标准化预测分布误差对最终模型进行评估。鉴于有证据表明躁狂症患者与癫痫患者的丙戊酸清除率存在差异，将结果与先前报道的癫痫患者结果进行了比较。
丙戊酸数据用单室模型能得到充分描述。丙戊酸清除率的显著预测因素包括丙戊酸剂量和体重。丙戊酸的群体CL/F和V/F估计值分别为0.464 L/h和23.3 L。本研究获得的丙戊酸清除率似乎与癫痫患者的清除率无显著差异。
建立了合格的躁狂症患者丙戊酸群体药代动力学模型。该模型可用于优化躁狂症患者的丙戊酸治疗。丙戊酸清除率可根据患者的丙戊酸剂量和体重进行预测。这种预测的清除率随后可用于个体化确定最佳丙戊酸维持剂量。
