DOSE PROPORTIONALITY OF CISATRACURIUM

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.