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Pharmacokinetic‐Pharmacodynamic Modeling of Atracurium in Intensive Care Patients
Author(s) -
Farenc Christine,
Lefrant JeanYves,
Audran Michel,
Bressolle Françoise
Publication year - 2001
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912700122009827
Subject(s) - pharmacokinetics , pharmacodynamics , medicine , mechanical ventilation , volume of distribution , anesthesia , atracurium besilate , elimination rate constant , bolus (digestion) , intensive care , pharmacology , surgery , neuromuscular blockade , intensive care medicine
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, γ, was 4.04. The concentration producing 50% of the E max was 1.36 μg/mL, and the mean k e0 was 0.059 min −1 . Recovery time ranged from 30 to 80 minutes, and none of the patients of this study had residual paralysis.