title: Pharmacokinetics and pharmacodynamics of cisatracurium in patients with end-stage liver disease undergoing liver transplantation.
abstract: We determined the pharmacokinetics and pharmacodynamics of cisatracurium, one of the 10 isomers of atracurium, in 14 patients with end-stage liver disease undergoing liver transplantation and in 11 control patients with normal hepatic and renal function undergoing elective surgery. Blood samples were collected for 8 h after i.v. bolus administration of cisatracurium 0.1 mg kg-1 (2 x ED95). Plasma concentrations of cisatracurium and its metabolites were determined using an HPLC method with fluorescence detection. Pharmacokinetic variables were determined using non-compartmental methods. Neuromuscular block was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve using a Puritan-Bennett Datex (Helsinki, Finland) monitor. Pharmacodynamic modelling was completed using semi-parametric effect-compartment analysis. Volume of distribution at steady state was 195 (SD 38) ml kg-1 in liver transplant patients and 161 (23) ml kg-1 in control patients (P < 0.05), plasma clearance was 6.6 (1.1) ml kg-1 min-1 in liver transplant patients and 5.7 (0.8) ml kg-1 min-1 in control patients (P < 0.05), but elimination half-lives were similar: 24.4 (2.9) min in liver transplant patients vs 23.5 (3.5) min in control patients (ns). The time to maximum block was 2.4 (0.8) min in liver transplant patients compared with 3.3 (1.0) min in control patients (P < 0.05), but the clinical effective duration of action (time to 25% recovery) was similar: 53.5 (11.9) min in liver transplant patients compared with 46.9 (6.9) min in control patients (ns). The recovery index (25-75% recovery) was also similar in both groups: 15.4 (4.2) min in liver transplant patients and 12.8 (1.9) min in control patients (ns). After cisatracurium, peak laudanosine concentrations were 16 (5) and 21 (5) ng ml-1 in liver transplant and control patients, respectively. In summary, minor differences in the pharmacokinetics and pharmacodynamics of cisatracurium in liver transplant and control patients were not associated with any clinically significant differences in recovery profiles after a single dose of cisatracurium.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh School of Medicine, PA, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: De Wolf
authors.forename: J A
authors.initials: JA
authors.lastname: Freeman
authors.forename: V L
authors.initials: VL
authors.lastname: Scott
authors.forename: W
authors.initials: W
authors.lastname: Tullock
authors.forename: D A
authors.initials: DA
authors.lastname: Smith
authors.forename: D F
authors.initials: DF
authors.lastname: Kisor
authors.forename: S
authors.initials: S
authors.lastname: Kerls
authors.forename: D R
authors.initials: DR
authors.lastname: Cook
mesh_terms: D000328:Adult; D000368:Aged; D001279:Atracurium / Q000493:pharmacokinetics*; D005071:Evoked Potentials; D005260:Female; D006207:Half-Life; D006801:Humans; D007536:Isomerism; D007546:Isoquinolines / Q000097:blood; D017093:Liver Failure / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009469:Neuromuscular Junction / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D013997:Time Factors
chemical_list: D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D001279:Atracurium; C001522:laudanosine