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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 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 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 E(max) 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.

journal_name

Acta Pharmacol Sin

journal_title

Acta pharmacologica Sinica

authors

Li YH,Wu FS,Xu JG

doi

10.1111/j.1745-7254.2006.00309.x

subject

Has Abstract

pub_date

2006-05-01 00:00:00

pages

629-34

issue

5

eissn

1671-4083

issn

1745-7254

journal_volume

27

pub_type

杂志文章

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