Pharmacokinetics and pharmacodynamics of cisatracurium in patients with end-stage liver disease undergoing liver transplantation |
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| Authors: | De Wolf, A. M. Freeman, J. A. Scott, V. L. Tullock, W. Smith, D. A. Kisor, D. F. Kerls, S. Cook, D. R. |
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| Affiliation: | Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Clinical Pharmacokinetics/Dynamics, Glaxo Wellcome, Research Triangle Park, NC, USA; Division of Pharmacokinetics and Drug Metabolism, Glaxo Wellcome, Research Triangle Park, NC, USA; Department of Clinical Neurosciences, Glaxo Wellcome, Research Triangle Park, NC, USA |
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| Abstract: | We determined the pharmacokinetics and pharmacodynamics of cisatracurium,one of the 10 isomers of atracurium, in 14 patients with end-stage liverdisease undergoing liver transplantation and in 11 control patients withnormal hepatic and renal function undergoing elective surgery. Bloodsamples were collected for 8 h after i.v. bolus administration ofcisatracurium 0.1 mg kg-1 (2 x ED95). Plasma concentrations ofcisatracurium and its metabolites were determined using an HPLC method withfluorescence detection. Pharmacokinetic variables were determined usingnon-compartmental methods. Neuromuscular block was assessed by measuringthe electromyographic evoked response of the adductor pollicis muscle totrain-of-four stimulation of the ulnar nerve using a Puritan-Bennett Datex(Helsinki, Finland) monitor. Pharmacodynamic modelling was completed usingsemi- parametric effect-compartment analysis. Volume of distribution atsteady 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-1min-1 in control patients (P < 0.05), but elimination half-lives weresimilar: 24.4 (2.9) min in liver transplant patients vs 23.5 (3.5) min incontrol patients (ns). The time to maximum block was 2.4 (0.8) min in livertransplant 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 with46.9 (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 livertransplant patients and 12.8 (1.9) min in control patients (ns). Aftercisatracurium, peak laudanosine concentrations were 16 (5) and 21 (5) ngml-1 in liver transplant and control patients, respectively. In summary,minor differences in the pharmacokinetics and pharmacodynamics ofcisatracurium in liver transplant and control patients were not associatedwith any clinically significant differences in recovery profiles after asingle dose of cisatracurium. |
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