Pharmacokinetic and pharmacodynamic modelling with pancuronium. 1984

M A Evans, and C A Shanks, and K F Brown, and E J Triggs

The pharmacokinetics and pharmacodynamics of pancuronium were studied following intravenous infusion in eleven patients undergoing surgical anaesthesia. Measurement of the plasma concentrations (Cp) of the neuromuscular blocking agent ( NMBA ) and the concomitant intensities of paralysis allowed their simultaneous modelling. The pharmacokinetic parameters derived for pancuronium were in the range of previously reported values, except that the mean total systemic plasma clearance (0.79 +/- 0.28 ml X min-1 X kg-1) was reduced and the mean terminal phase half-life (169 min) was longer in these patients. Plasma concentration and % paralysis data were successfully fitted to a previously proposed pharmacodynamic model. This model assumes a separate effect compartment which exchanges drug directly with the central kinetic compartment (integrated effect model). The 'steady-state' Cp necessary to produce 50% paralysis ( ECpss (50] was estimated to be 0.21 +/- 0.08 micrograms X ml-1 (mechanical response) and 0.18 +/- 0.05 micrograms X ml-1 (EMG response). An analysis using the Hill equation of the Cp-response relationship, during and after the constant-rate infusion of pancuronium bromide, resulted in effective plasma concentrations for 50% paralysis ( ECp50 ) of 0.35 +/- 0.06 micrograms X ml-1 and 0.20 +/- 0.09 micrograms X ml-1, respectively, for mechanical twitch response. The corresponding values for EMG response were 0.32 +/- 0.06 micrograms X ml-1 and 0.17 +/- 0.06 micrograms X ml-1. Using this latter approach, the ECp50 estimated during onset of paralysis was significantly higher than that estimated during offset of paralysis (p less than 0.05); no such difference was apparent between this latter parameter and the ECpss (50) of the integrated effect model (p greater than 0.05). No significant differences were observed between any of the pharmacodynamic parameter estimates generated from the data obtained from the two methods of assessment of neuromuscular function (mechanical vs. EMG response) (p greater than 0.05).

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009469 Neuromuscular Junction The synapse between a neuron and a muscle. Myoneural Junction,Nerve-Muscle Preparation,Junction, Myoneural,Junction, Neuromuscular,Junctions, Myoneural,Junctions, Neuromuscular,Myoneural Junctions,Nerve Muscle Preparation,Nerve-Muscle Preparations,Neuromuscular Junctions,Preparation, Nerve-Muscle,Preparations, Nerve-Muscle
D010197 Pancuronium A bis-quaternary steroid that is a competitive nicotinic antagonist. As a neuromuscular blocking agent it is more potent than CURARE but has less effect on the circulatory system and on histamine release. Pancuronium Bromide,Pancuronium Curamed,Pancuronium Organon,Pavulon,Bromide, Pancuronium
D004576 Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Electromyogram,Surface Electromyography,Electromyograms,Electromyographies,Electromyographies, Surface,Electromyography, Surface,Surface Electromyographies
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults

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