Rapado, Javier., Fabregas, Neus., Valero, Ricard., Carrero, Enrique., Gambús, Pedro., Trocóniz, Iñaki
Department of Pharmacy, School of Pharmacy, University of Navarra, Pamplona 31080 Spain, and Department of Anesthesiology; Clinic Hospital; Villarroel 170, Barcelona 08036, Spain
Population pharmacokinetic/pharmacodynamic modelling approach was used to characterize the sedation and airway obstruction effects of propofol administered in a target controlled infusion system to rapidly achieve and maintain a (predicted) concentration of 1mg/L. Twenty-one subjects with advanced parkinson disease undergoing functional stereotactic surgery were included in the study. Blood samples, sedation score according to the Ramsay sedation scale and the degree of airway obstruction according to a standard scale were recorded 10 minutes after each new propofol target level was achieved to ensure steady-state distribution conditions at the site of effect.
The kinetics of propofol in plasma was modelled nonparametrically using linear interpolation. The sedation and airway obstruction scores were treated as ordered categorical response variables and were analyzed using a logistic regression model with the non-linear mixed effect modelling approach.
Both response variables were best described relating effect site concentrations (Ce) with drug effects using an Emax model. Pharmacodynamic estimates were: Emax, 8.7 and 7.4; C50, 0.4 and 0.35 mg/L; and ke0, 0.4 and 0.3 1/min, for the sedation and airway obstruction effects, respectively. Despite of the similarities in the pharmacodynamic estimates, the differences found in the baseline parameters between the two response variables resulted in marked differences in their probability of getting a certain score vs Ce profiles: Sedation can be achieved at low concentrations of propofol, whereas the probability of achieving a moderate airway obstruction is negligible at those low concentrations.
Reference: PAGE 10 (2001) Abstr 225 [www.page-meeting.org/?abstract=225]
Poster: poster