Pharmacokinetics and pharmacodynamics of cisatracurium after a short infusion in patients under propofol anesthesia.
Fourteen patients, ASA physical status I or II, were recruited to assess the pharmacokinetic-pharmacodynamic relationship of cisatracurium under nitrous oxide/sufentanil/propofol anesthesia. The electromyographic response of the abductor digiti minimi muscle was recorded on train-of-four stimulation of the ulnar nerve. A 0.1-mg/kg dose of cisatracurium was given as an infusion over 5 min. Arterial plasma concentrations of cisatracurium and its major metabolites were measured by using high-performance liquid chromatography. A nontraditional two-compartment pharmacokinetic model with elimination from central and peripheral compartments was used. The elimination rate constant from the peripheral compartment was fixed to the in vitro rate of degradation of cisatracurium in human plasma (0.0237 min(-1)). The mean terminal half-life of cisatracurium was 23.9+/-3.3 min, and its total clearance averaged 3.7+/-0.8 mL x min(-1) x kg(-1). Using this model, the volume of distribution at steady state was significantly increased compared with that obtained when central elimination only was assumed (0.118+/-0.027 vs 0.089+/-0.017 L/kg). The effect-plasma equilibration rate constant was 0.054+/-0.013 min(-1). The 50% effective concentration (153+/-33 ng/mL) was 56% higher than that reported in patients anesthetized with volatile anesthetics, which suggests that, compared with inhaled anesthetics, a cisatracurium neuromuscular block is less enhanced by propofol.


CONCLUSIONS
The drug concentration-effect relationship of the muscle relaxant cisatracurium has been characterized under balanced and isoflurane anesthesia. Because propofol is now widely used as an IV anesthetic, it is important to characterize the biological fate and the concentration-effect relationship of cisatracurium under propofol anesthesia as well.
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Faculté de Pharmacie, Université de Montréal, Québec, Canada.
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous / Q000009:adverse effects*; D019540:Area Under Curve; D001279:Atracurium / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004576:Electromyography; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009466:Neuromuscular Blocking Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015742:Propofol / Q000009:adverse effects*
D018686:Anesthetics, Intravenous; D009466:Neuromuscular Blocking Agents; D001279:Atracurium; C101584:cisatracurium; D015742:Propofol