Pharmacokinetics/pharmacodynamics of cisatracurium in healthy adult patients

The pharmacokinetics of cisatracurium and its metabolites were evaluated in 56 healthy adult surgical patients with full sampling (17 blood samples collected over 8 h) after single intravenous bolus doses of cisatracurium and in 186 healthy adult surgical patients with sparse sampling (five to eight blood samples collected randomly over 2 h) after single intravenous bolus doses with or without maintenance doses or continuous infusions of cisatracurium. Plasma concentration-time and neuromuscular block data from the patients with full sampling were analyzed using compartmental and non-compartmental pharmacokinetic models and semiparametric effect compartment analyses. Data from all patients were pooled to determine the population pharmacokinetics/pharmacodynamics of cisatracurium. Results from in vitro and in vivo studies indicated that Hofmann elimination is the predominant pathway for the elimination of cisatracurium in humans. The pharmacokinetics of cisatracurium are independent of the dose from 0.1 to 0.4 mg/kg [two to eight times the dose producing 95% suppression (ED95) of the first evoked twitch response of the adductor pollicis muscle to a train of four stimulations]. Anaesthesia type, sex, estimated creatinine clearance and the presence of obesity were associated with statistically significant effects on the pharmacokinetic/pharmacodynamic parameters for cisatracurium. These covariates were not associated with any clinically significant changes in the predicted recovery profile of cisatracurium. Slight differences in onset were predicted in patients with renal impairment and in patients given inhalation anaesthesia.