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Aim:To determine propofol concentration in the cerebral spinal fluid (CSF) ofneurosurgical patients and carry out a preliminary population pharmacodynamicstudy.Methods:Twenty-seven elective neurosurgical patients (12 men and 15women) aged 17-74 years received propofol in a bolus dose of 2 mg/kg for 5 minand an infusion of 10 mg/kg per h for 5 min.Frequent CSF samples were drawn andassayed for propofol concentration.The bispectral index (BIS) was used to mea-sure the drug effect.All data were analyzed first with the Excel software package,then pharmacodynamics modeling was performed using the NONMEM softwarepackage.Results:The CSF concentration was related to the drug effect withlinear and sigmoid E_(max) models.The parameters for the linear addictive modelwere a= 1.11 and b=95.4.The parameters for the linear exponential model were a=1.05 and b=92.7.The parameters for the sigmoid E_(max) model were E_(max)=119,EC_(50)=53.6ng/mL,and N=1.51.When the covariates of age,weight and sex wereconsidered,the parameters of models,objective function,the standard error of themean and the prediction error were not optimized.Conclusion:Linear additive,linear exponential and sigmoid E_(max) models can be used to describe the pharmaco-dynamics of propofol with respect to the concentration in CSF.In this smallpopulation,age (17-74 years),weight (47-98kg) and sex did not influence any ofthe pharmacodynamic parameters of propofol.To verify these preliminary results,a larger study population is required.
Aim: To determine propofol concentration in the cerebral spinal fluid (CSF) of urosurgical 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 mea-sure the drug effect. All data was 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 E_max models.The parameters for the linear addictive modelwere a = 1.11 and b = 95.4. The parameters for the linear exponential model were a = 1.05 and b = 92.7. The parameters for the sigmoid E max model were E max = 119, EC 50 = 53.6 ng / mL, and N = 1.51 .When the covariates of age, weight and sex wereco nsidered, the parameters of models, objective function, the standard error of themean and the prediction error were not optimized. Conlusion: Linear additive, linear exponential and sigmoid Emax models can be used to describe the pharmaco-dynamics of propofol with respect to the concentration in CSF. this smallpopulation, 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.