Influence of age and sex on pharmacodynamics of propofol in neurosurgical patients: Model development

Abstract

Aim: To determine propofol concentration in the cerebral spinal fluid (CSF) of neurosurgical patients and carry out a preliminary population pharmacodynamic study. Methods: Twenty-seven elective neurosurgical patients (12 men and 15 women) aged 17-74 years received propofol in a bolus dose of 2 mg/kg for 5 min and an infusion of 10 mg/kg per h for 5 min. Frequent CSF samples were drawn and assayed for propofol concentration. The bispectral index (BIS) was used to measure the drug effect. All data were analyzed first with the Excel software package, then pharmacodynamics modeling was performed using the NONMEM software package. Results: The CSF concentration was related to the drug effect with linear and sigmoid Emax models. The parameters for the linear addictive model were a=1.11 and b=95.4. The parameters for the linear exponential model were a= 1.05 andb=92.7. The parameters for the sigmoid Emax model were Emax=1 19, EC50= 53.6 ng/mL, and N=1.51. When the covariates of age, weight and sex were considered, the parameters of models, objective function, the standard error of the mean and the prediction error were not optimized. Conclusion: Linear additive, linear exponential and sigmoid Emax models can be used to describe the pharmacodynamics of propofol with respect to the concentration in CSF. In this small population, age (17-74 years), weight (47-98 kg) and sex did not influence any of the pharmacodynamic parameters of propofol. To verify these preliminary results, a larger study population is required. ©2006 CPS and SIMM.