Influence of extreme obesity on the body disposition and neuromuscular blocking effect of atracurium.
The pharmacokinetics and pharmacodynamics of atracurium, a nondepolarizing neuromuscular blocking agent, were compared between morbidly obese patients and nonobese patients. Atracurium besylate (0.2 mg/kg) was administered intravenously as a bolus to patients who had received anesthesia. The force of contraction of the adductor pollicis was measured and plasma samples were collected for a 2-hour period. The concentrations of atracurium and its major end product, laudanosine, were determined by use of a chromatographic method. The pharmacokinetic-pharmacodynamic relationship was characterized by use of several models. No difference was observed between obese patients and nonobese patients in atracurium elimination half-life (19.8 +/- 0.7 versus 19.7 +/- 0.7 minutes), volume of distribution at steady state (8.6 +/- 0.7 versus 8.5 +/- 0.7 L), and total clearance (444 +/- 29 versus 404 +/- 25 ml/min). However, if values were expressed on a total body weight basis, there was a difference between obese and nonobese patients in the volume of distribution at steady state (0.067 versus 0.141 L/kg) and total clearance (3.5 +/- 0.2 versus 6.6 +/- 0.5 ml/min/kg). Although atracurium concentrations were consistently higher in obese patients than in nonobese patients, there was no difference in the time of recovery from neuromuscular blockade between the two groups. Consequently, the median effective concentration was higher in obese than in nonobese patients (470 +/- 46 versus 312 +/- 33 ng/ml).
Varin
F
F
Faculté de Pharmacie, Université de Montréal, Québec, Canada.
Ducharme
J
J
Théorêt
Y
Y
Besner
J G
JG
Bevan
D R
DR
Donati
F
F
D000328:Adult; D001279:Atracurium / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009466:Neuromuscular Blocking Agents; D009767:Obesity, Morbid / Q000097:blood / Q000378:metabolism*
D007546:Isoquinolines; D009466:Neuromuscular Blocking Agents; D001279:Atracurium; C001522:laudanosine