Xingang Li1,2, Shusen Sun3, Xi Ling1, Kai Chen4, Qiang Wang5, Zhigang Zhao6,7. 1. Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Dongcheng District, Beijing, 100050, China. 2. Precision Medicine Research Center for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 3. College of Pharmacy, Western New England University, Springfield, MA, USA. 4. Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Dongcheng District, Beijing, 100050, China. 5. Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Dongcheng District, Beijing, 100050, China. ttyywq@163.com. 6. Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Dongcheng District, Beijing, 100050, China. 1022zzg@sina.com. 7. Precision Medicine Research Center for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 1022zzg@sina.com.
Abstract
PURPOSE: Combined intravenous and intraventricular administration of vancomycin into the cerebrospinal fluid (CSF) has been increasingly utilized for neurosurgical patients, but little is known about the population pharmacokinetics of vancomycin in the plasma and CSF. The aim of our study was to identify significant factors associated with plasma and CSF vancomycin concentrations to guide clinicians with vancomycin dosing. METHODS: Patients with an indwelling ventricular drainage catheter who received intravenous and intraventricular vancomycin were enrolled in this study. Blood and CSF samples were collected at scheduled times and vancomycin concentrations determined. A three-compartmental model (central, peripheral and CSF compartments) was proposed to describe the in vivo behavior of vancomycin. CSF outflow resulted in vancomycin loss, and the clearance of CSF compartment (CLCSF) was used to describe this loss. The nonlinear mixed-effects modeling method was applied to structure the population model, and the stepwise incorporation of seven covariates into the final model was attempted. Simulation was performed with the goal of CSF concentrations reaching or exceeding the minimum inhibitory concentration during therapy. RESULTS: Serum creatinine clearance had a significant influence on clearance of the central compartment. CLCSF had a positive correlation with drainage amount and a negative correlation with elapsed time. Model validation (bootstrap and visual predictive check) demonstrated the stability and performance of the proposed population model. A simple-to-use dosage regimen table was created based on the simulation results. CONCLUSIONS: The proposed final model may be used to guide clinicians with vancomycin dosing in this specific patient population.
PURPOSE: Combined intravenous and intraventricular administration of vancomycin into the cerebrospinal fluid (CSF) has been increasingly utilized for neurosurgical patients, but little is known about the population pharmacokinetics of vancomycin in the plasma and CSF. The aim of our study was to identify significant factors associated with plasma and CSF vancomycin concentrations to guide clinicians with vancomycin dosing. METHODS:Patients with an indwelling ventricular drainage catheter who received intravenous and intraventricular vancomycin were enrolled in this study. Blood and CSF samples were collected at scheduled times and vancomycin concentrations determined. A three-compartmental model (central, peripheral and CSF compartments) was proposed to describe the in vivo behavior of vancomycin. CSF outflow resulted in vancomycin loss, and the clearance of CSF compartment (CLCSF) was used to describe this loss. The nonlinear mixed-effects modeling method was applied to structure the population model, and the stepwise incorporation of seven covariates into the final model was attempted. Simulation was performed with the goal of CSF concentrations reaching or exceeding the minimum inhibitory concentration during therapy. RESULTS: Serum creatinine clearance had a significant influence on clearance of the central compartment. CLCSF had a positive correlation with drainage amount and a negative correlation with elapsed time. Model validation (bootstrap and visual predictive check) demonstrated the stability and performance of the proposed population model. A simple-to-use dosage regimen table was created based on the simulation results. CONCLUSIONS: The proposed final model may be used to guide clinicians with vancomycin dosing in this specific patient population.
Authors: Michael Rybak; Ben Lomaestro; John C Rotschafer; Robert Moellering; William Craig; Marianne Billeter; Joseph R Dalovisio; Donald P Levine Journal: Am J Health Syst Pharm Date: 2009-01-01 Impact factor: 2.637
Authors: Jennifer H Martin; Ross Norris; Michael Barras; Jason Roberts; Ray Morris; Matthew Doogue; Graham R D Jones Journal: Clin Biochem Rev Date: 2010-02
Authors: IfeanyiChukwu O Onor; Alison Neuliep; Kieu Anh Tran; Jennifer Lambert; Christopher J Gillard; Fatima Brakta; Michael C Ezebuenyi; Kirbie St James; John I Okogbaa; Robbie A Beyl Journal: Drugs R D Date: 2020-06