Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku and Turku University Hospital, Turku, Finland.
Br J Anaesth. 2012 Mar;108(3):460-8. doi: 10.1093/bja/aer441. Epub 2012 Jan 25.
Dexmedetomidine is a highly selective and potent α(2)-adrenoceptor agonist registered for sedation of patients in intensive care units. There is little information on factors possibly affecting its pharmacokinetics during long drug infusions in critically ill patients. We characterized the pharmacokinetics of dexmedetomidine in critically ill patients during long-term sedation using a population pharmacokinetic approach.
Twenty-one intensive care patients requiring sedation and mechanical ventilation received dexmedetomidine with a loading dose of 3-6 µg kg(-1) h(-1) in 10 min and a maintenance dose of 0.1-2.5 µg kg(-1) h(-1) for a median duration of 96 h (range, 20-571 h). Cardiac output (CO), laboratory and respiratory parameters, and dexmedetomidine concentrations in arterial plasma were measured. The pharmacokinetics was determined by population analysis using linear multicompartment models.
The pharmacokinetics of dexmedetomidine was best described by a two-compartment model. The population values (95% confidence interval) for elimination clearance, inter-compartmental clearance, central volume of distribution, and volume of distribution at steady state were 57.0 (42.1, 65.6), 183 (157, 212) litre h(-1), 12.3 (7.6, 17.0), and 132 (96, 189) litre. Dexmedetomidine clearance decreased with decreasing CO and with increasing age, whereas its volume of distribution at steady state was increased in patients with low plasma albumin concentration.
The population pharmacokinetics of dexmedetomidine was generally in line with results from previous studies. In elderly patients and in patients with hypoalbuminaemia, the elimination half-life and the context-sensitive half-time of dexmedetomidine were prolonged.
右美托咪定是一种高度选择性和有效的 α（2）-肾上腺素能受体激动剂，已注册用于重症监护病房患者的镇静。关于可能影响其在危重病患者中长时间输注时药代动力学的因素，信息很少。我们采用群体药代动力学方法描述了长时间镇静期间右美托咪定在危重病患者中的药代动力学。
21 例需要镇静和机械通气的重症监护患者接受右美托咪定负荷剂量 3-6μgkg（-1）h（-1），持续 10 分钟，维持剂量 0.1-2.5μgkg（-1）h（-1），中位数时间为 96 小时（范围，20-571 小时）。测量心输出量（CO）、实验室和呼吸参数以及动脉血浆中的右美托咪定浓度。采用线性多室模型进行群体分析来确定药代动力学。
右美托咪定的药代动力学最好用两室模型描述。消除清除率、隔室清除率、中央分布容积和稳态分布容积的群体值（95%置信区间）分别为 57.0（42.1，65.6）、183（157，212）升小时（-1）、12.3（7.6，17.0）和 132（96，189）升。右美托咪定清除率随 CO 降低和年龄增加而降低，而稳态时的分布容积在低血浆白蛋白浓度的患者中增加。
右美托咪定的群体药代动力学通常与先前研究的结果一致。在老年患者和低白蛋白血症患者中，右美托咪定的消除半衰期和浓度时间依赖性半衰期延长。
