Service de Pharmacologie Médicale et Clinique APHM, Aix Marseille Université, Marseille, France.
Eur J Clin Pharmacol. 2013 Sep;69(9):1667-72. doi: 10.1007/s00228-013-1527-3. Epub 2013 May 30.
Thiopental is a thiobarbiturate given in the case of brain injuries to reduce intracranial pressure and to manage cerebral ischemia. A pharmacokinetic model has been described previously in critically ill patients with a different therapeutic strategy. New treatment options prompted us to investigate if drug-drug interactions occur. A new model is proposed describing the influence of concomitant administration of esomeprazole on the distribution of thiopental.
The study population comprised 52 critically ill patients (body weight 47.1-114 kg) aged 18-78 years who had been admitted into the critical care unit for treatment of intracranial hypertension. A total mean dose of 282.8 ± 172.7 mg/kg was given in 96 ± 72 h. Pharmacokinetic analysis was performed by using a nonlinear mixed-effect population model.
A one-compartment open model with first-order elimination identified two covariates, namely, body weight on clearance and volume of distribution, and the administration of esomeprazole on volume of distribution. The mean values (% relative standard error) for total clearance (CL) and for central volume of distribution (Vd) in patients with and without concomitant esomeprazole were 5.3 L/h (9.2 %) and 256.1 (6.4 %) and 153.2 l (19.2 %), respectively.
Based on these results, we conclude that concomitant administration of esomeprazole increases the volume of distribution and the half-live of thiopental. This drug-drug interaction should be considered when a target concentration has to be reached.
硫喷妥钠是一种硫代巴比妥酸盐，用于治疗脑损伤以降低颅内压和治疗脑缺血。先前已经在采用不同治疗策略的危重病患者中描述了药代动力学模型。新的治疗选择促使我们研究是否存在药物相互作用。提出了一个新的模型来描述伴随给予埃索美拉唑对硫喷妥钠分布的影响。
研究人群包括 52 名年龄在 18-78 岁的重症患者（体重 47.1-114 公斤），他们因颅内高压而入住重症监护病房接受治疗。在 96±72 小时内给予了 282.8±172.7mg/kg 的平均总剂量。通过非线性混合效应群体模型进行药代动力学分析。
一个具有一级消除的单室开放模型确定了两个协变量，即清除率的体重和分布容积，以及埃索美拉唑的给予对分布容积的影响。伴有和不伴有伴随埃索美拉唑的患者的总清除率（CL）和中央分布容积（Vd）的平均值（%相对标准误差）分别为 5.3 L/h（9.2%）和 256.1（6.4%）和 153.2 l（19.2%）。
基于这些结果，我们得出结论，伴随给予埃索美拉唑会增加硫喷妥钠的分布容积和半衰期。在需要达到目标浓度时，应考虑这种药物相互作用。
