Pharmacokinetic-pharmacodynamic modeling of atracurium in intensive care patients.
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.
Farenc
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Laboratoire de Pharmacocinétique Clinique, Faculté de Pharmacie 34060 Montpellier, France.
Lefrant
J Y
JY
Audran
M
M
Bressolle
F
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001279:Atracurium / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D016638:Critical Illness; D004334:Drug Administration Schedule; D006801:Humans; D007262:Infusions, Intravenous; D007546:Isoquinolines / Q000493:pharmacokinetics; D008875:Middle Aged; D008954:Models, Biological; D003473:Neuromuscular Nondepolarizing Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000378:metabolism*
D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D001279:Atracurium; C001522:laudanosine