Clinical pharmacokinetics of cisatracurium besilate

Cisatracurium besilate, one of the 10 stereoisomers that comprise atracuriu m besilate, is a nondepolarising neuromuscular blocking agent with an inter mediate duration of action. Following a 5- to 10-sec intravenous bolus dose of cisatracurium besilate to healthy young adult surgical patients, elderl y patients and patients with renal or hepatic failure, the concentration ve rsus time profile of of cisatracurium besilate is best characterised by a 2 -compartment model. The volume of distribution (Vd) of cisatracurium besila te is small because of its relatively large molecular weight and high polar ity. Cisatracurium besilate undergoes Hofmann elimination, a process dependent o n pH and temperature. Unlike atracurium besilate, cisatracurium besilate do es not appear to be degraded directly by ester hydrolysis. Hofmann eliminat ion, an organ independent elimination pathway, occurs in plasma and tissue, and is responsible for approximately 77% of the overall elimination of cis atracurium besilate. The total body clearance (CL), steady-state Vd and elimination half-life of cisatracurium besilate in patients with normal organ function are approxim ately 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 besil ate is low (16%), a finding consistent with the strict physiological contro l of the factors that effect the Hofmann elimination of cisatracurium besil ate (i.e, temperature and pH). There is a unique relationship between plasm a clearance and Vd because the primary elimination pathway fur cisatracuriu m besilate is not dependent on organ function. There are ruiner differences in the pharmacokinetics of cisatracurium besil ate in various patient populations. These differences are not associated wi th clinically significant differences in the recovery profile of cisatracur ium besilate, but may be associated with differences in the time to onset o f neuromuscular block.