Pharmacokinetic-pharmacodynamic modeling of atracurium in intensive care patients

J Clin Pharmacol. 2001 Jan;41(1):44-50. doi: 10.1177/00912700122009827.

Abstract

The authors have studied 10 critically ill patients with acute respiratory distress syndrome who required a neuromuscular blocking drug to assist mechanical ventilation. Patients received a bolus dose of 1 mg/kg of atracurium followed by a constant infusion rate of 1 mg/kg/h of this drug for 72 hours. Neuromuscular block was monitored using an accelerograph. Blood samples were obtained over a 96-hour period. A preliminary independent analysis was done to estimate the individual pharmacokinetic parameters; data were consistent with a one-compartment model. The pharmacodynamic data analysis was then performed using the changes in train-of-four (TOF) count as an index of the therapeutic effect of atracurium. Pharmacokinetic-dynamic variables were calculated using the Sheiner model and the Hill equation. The elimination half-life of atracurium averaged 22 minutes. Mean volume of distribution and plasma clearance were 217 ml/kg and 550 ml/min, respectively. There was a significant hysteresis loop when the TOF count was plotted against predicted plasma atracurium concentrations. The mean sigmoidicity factor, gamma, was 4.04. The concentration producing 50% of the Emax was 1.36 micrograms/mL, and the mean ke0 was 0.059 min-1. Recovery time ranged from 30 to 80 minutes, and none of the patients of this study had residual paralysis.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Atracurium / blood
  • Atracurium / pharmacokinetics*
  • Atracurium / pharmacology
  • Critical Illness
  • Drug Administration Schedule
  • Humans
  • Infusions, Intravenous
  • Isoquinolines / pharmacokinetics
  • Middle Aged
  • Models, Biological*
  • Neuromuscular Nondepolarizing Agents / blood
  • Neuromuscular Nondepolarizing Agents / pharmacokinetics*
  • Neuromuscular Nondepolarizing Agents / pharmacology
  • Respiration, Artificial
  • Respiratory Distress Syndrome / blood
  • Respiratory Distress Syndrome / metabolism*

Substances

  • Isoquinolines
  • Neuromuscular Nondepolarizing Agents
  • Atracurium
  • laudanosine