Dose proportionality of cisatracurium.
The dose proportionality of cisatracurium pharmacokinetics was assessed using a population approach by incorporating the collection of sparse blood samples from patients in clinical trials. Plasma concentration-time data from 131 patients with limited concentration-time data and 38 patients with full sampling were pooled and analyzed using nonlinear mixed-effects modeling (NONMEM). Dose proportionality was assessed using dichotomous parameterization and a linear model. The population pharmacokinetic approach revealed that the pharmacokinetics of cisatracurium are independent of dose between 0.1 mg/kg and 0.4 mg/kg, as was expected based on the importance of Hofmann elimination, a chemical process dependent on pH and temperature.
Schmith
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VD
Glaxo Wellcome, Inc., Research Triangle Park, North Carolina 27709, USA.
Fiedler-Kelly
J
J
Phillips
L
L
Grasela
T H
TH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001279:Atracurium / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008875:Middle Aged; D009466:Neuromuscular Blocking Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*
D009466:Neuromuscular Blocking Agents; D001279:Atracurium; C101584:cisatracurium