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.

By, Schmith VD, Jill Fiedler-Kelly, Phillips L, Thaddeus H Grasela