The dose proportionality of cisatracurium pharmacokinetics was assesse
d using a population approach by incorporating the collection of spars
e 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 nonlinea
r mixed-effects modeling (NONMEM). Dose proportionality was assessed u
sing dichotomous parameterization and a linear model. The population p
harmacokinetic approach revealed that the pharmacokinetics of cisatrac
urium 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 pr
ocess dependent on pH and temperature.