关键词: 万古霉素, 神经外科, 群体药代动力学, 脑脊液, 治疗药物监测

Abstract:

AIM: To establish the population pharmacokinetic model of vancomycin in post-operative neurosurgical patients and to provide information for precision medicine. METHODS: A total of 56 neurosurgical patients with external ventricular drainage were enrolled in this study. Vancomycin was intravenously administered into the patients and blood and cerebrospinal fluid samples were obtained at the scheduled time. Nonlinear mixed-effects modeling method was applied to develop population pharmacokinetic model. Goodness-of-fit, bootstrap and visual predictive check were employed to test the final model.RESULTS:Three-compartmental model (central, peripheral and cerebrospinal fluid compartments) was applied to describe the vancomycin model. The cerebrospinal fluid cell count could significantly affect the clearance between central and cerebrospinal fluid compartments (Qcsf), and the positive relationship was observed between the drainage amount and clearance of cerebrospinal fluid compartment (CLcsf). The estimated values of the model were similar to the median of bootstrap, and they are included in the 95% confidence interval. Bootstrap and visual predictive check demonstrated the stability and performance of the proposed population model. CONCLUSION: The proposed final model can be used to guide clinicians with vancomycin dosing in this specific patient population.

Key words: vancomycin, neurosurgical patients, population pharmacokinetics, cerebrospinal fluid, therapeutic drug monitoring