Kisor D F, Schmith V D
Department of Pharmacy Practice, College of Pharmacy, Ohio Northern University, Ada, USA.
Clin Pharmacokinet. 1999 Jan;36(1):27-40. doi: 10.2165/00003088-199936010-00003.
Cisatracurium besilate, one of the 10 stereoisomers that comprise atracurium besilate, is a nondepolarising neuromuscular blocking agent with an intermediate duration of action. Following a 5- to 10-sec intravenous bolus dose of cisatracurium besilate to healthy young adult surgical patients, elderly patients and patients with renal or hepatic failure, the concentration versus time profile of cisatracurium besilate is best characterised by a 2-compartment model. The volume of distribution (Vd) of cisatracurium besilate is small because of its relatively large molecular weight and high polarity. Cisatracurium besilate undergoes Hofmann elimination, a process dependent on pH and temperature. Unlike atracurium besilate, cisatracurium besilate does not appear to be degraded directly by ester hydrolysis. Hofmann elimination, an organ independent elimination pathway, occurs in plasma and tissue, and is responsible for approximately 77% of the overall elimination of cisatracurium besilate. The total body clearance (CL), steady-state Vd and elimination half-life of cisatracurium besilate in patients with normal organ function are approximately 0.28 L/h/kg (4.7 ml/min/kg), 0.145 L/kg and 25 minutes, respectively. The magnitude of interpatient variability in the CL of cisatracurium besilate is low (16%), a finding consistent with the strict physiological control of the factors that effect the Hofmann elimination of cisatracurium besilate (i.e. temperature and pH). There is a unique relationship between plasma clearance and Vd because the primary elimination pathway for cisatracurium besilate is not dependent on organ function. There are minor differences in the pharmacokinetics of cisatracurium besilate in various patient populations. These differences are not associated with clinically significant differences in the recovery profile of cisatracurium besilate, but may be associated with differences in the time to onset of neuromuscular block.
顺式苯磺酸阿曲库铵是组成苯磺酸阿曲库铵的10种立体异构体之一，是一种中效非去极化型神经肌肉阻滞剂。给健康的年轻成年手术患者、老年患者以及肾功能或肝功能衰竭患者静脉推注5至10秒的顺式苯磺酸阿曲库铵后，顺式苯磺酸阿曲库铵的浓度-时间曲线最适合用二室模型来描述。由于其相对较大的分子量和高极性，顺式苯磺酸阿曲库铵的分布容积（Vd）较小。顺式苯磺酸阿曲库铵进行霍夫曼消除，这一过程取决于pH值和温度。与苯磺酸阿曲库铵不同，顺式苯磺酸阿曲库铵似乎不会直接通过酯水解降解。霍夫曼消除是一种不依赖器官的消除途径，发生在血浆和组织中，约占顺式苯磺酸阿曲库铵总体消除的77%。器官功能正常的患者中，顺式苯磺酸阿曲库铵的总体清除率（CL）、稳态Vd和消除半衰期分别约为0.28 L/h/kg（4.7 ml/min/kg）、0.145 L/kg和25分钟。顺式苯磺酸阿曲库铵CL的患者间变异性较小（16%），这一发现与影响顺式苯磺酸阿曲库铵霍夫曼消除的因素（即温度和pH值）受到严格生理控制一致。血浆清除率和Vd之间存在独特的关系，因为顺式苯磺酸阿曲库铵的主要消除途径不依赖器官功能。不同患者群体中顺式苯磺酸阿曲库铵的药代动力学存在微小差异。这些差异与顺式苯磺酸阿曲库铵恢复情况的临床显著差异无关，但可能与神经肌肉阻滞起效时间的差异有关。
