Cooper Joyce M, Duffull Stephen B, Saiao Ana S, Isbister Geoffrey K
Faculty of Health & Medicine, University of Newcastle, Newcastle, New South Wales, Australia.
Br J Clin Pharmacol. 2015 Feb;79(2):307-15. doi: 10.1111/bcp.12500.
To investigate the pharmacokinetics (PK) of sertraline in overdose and the effect of single dose activated charcoal (SDAC).
Patients presenting to a toxicology unit with sertraline overdoses had demographic and clinical information recorded, and serial serum collected for measurement of sertraline concentrations. Monolix® version 4.2 was used to develop a population PK model of sertraline overdose and the effect of SDAC. Uncertainty in dose time was accounted for by shifting dose time using lag time with between subject variability (BSV). BSV on relative fraction absorbed was used to model uncertainty in dose.
There were 77 timed sertraline concentrations measured in 28 patients with sertraline overdoses with a median dose of 1550 mg (250-5000 mg). SDAC was given to seven patients between 1.5 and 4 h post-overdose. A one compartment model with lag time of 1 h and first order input and elimination adequately described the data. Including BSV on both lag time and relative fraction absorbed improved the model. The population PK parameter estimates for absorption rate constant, volume of distribution and clearance were 0.895 h(-1) , 5340 l and 130 l h(-1) , respectively. The calculated half-life of sertraline following overdose was 28 h (IQR 19.4-30.6h). When given up to 4 h post-overdose, SDAC significantly increased the clearance of sertraline by a factor of 1.9, decreased the area under the curve and decreased the maximum plasma concentration (Cmax ).
Sertraline had linear kinetics in overdose with parameter values similar to those in therapeutic use. SDAC is effective in increasing clearance when given 1.5 to 4 h post-overdose.
研究过量服用舍曲林后的药代动力学（PK）以及单剂量活性炭（SDAC）的作用。
收治到毒理学科室的舍曲林过量患者记录其人口统计学和临床信息，并采集系列血清样本以测定舍曲林浓度。使用Monolix® 4.2版软件建立舍曲林过量及SDAC作用的群体PK模型。通过使用滞后时间并结合个体间变异性（BSV）来移动给药时间，以考虑给药时间的不确定性。利用吸收相对分数的BSV来模拟剂量的不确定性。
28例舍曲林过量患者共测定了77个舍曲林浓度时间点，中位剂量为1550 mg（250 - 5000 mg）。7例患者在过量服药后1.5至4小时给予了SDAC。一个具有1小时滞后时间、一级输入和消除的单室模型能充分描述数据。纳入滞后时间和吸收相对分数的BSV可改善模型。吸收速率常数、分布容积和清除率的群体PK参数估计值分别为0.895 h⁻¹、5340 L和130 L/h。过量服用舍曲林后计算得出的半衰期为28小时（四分位间距19.4 - 30.6小时）。在过量服药后4小时内给予SDAC，可使舍曲林的清除率显著提高1.9倍，降低曲线下面积并降低最大血浆浓度（Cmax）。
舍曲林过量时具有线性动力学，参数值与治疗用药时相似。过量服药后1.5至4小时给予SDAC可有效提高清除率。
