title: Population Pharmacokinetics of Vancomycin in Postoperative Neurosurgical Patients.
abstract: Neurosurgical procedures may damage the blood-brain barrier to allow more vancomycin distribution into the cerebrospinal fluid (CSF) from blood after intravenous administration. However, a large intersubject variability in CSF vancomycin concentration was observed. We aimed to develop a population pharmacokinetic model to guide vancomycin dosing in patients after neurosurgical operation. Blood and CSF samples were collected and determined from postoperative neurosurgical patients after vancomycin administration. A three-compartment (central, peripheral, and CSF) model was proposed to characterize the pharmacokinetics of vancomycin. A nonlinear mixed-effects modeling approach was applied to fit the blood and CSF data simultaneously. The covariate analysis found that the CSF albumin level was strongly associated with the clearance between central and CSF compartment. Visual predictive check indicated that the proposed population pharmacokinetic model agrees well with the observed vancomycin concentrations. Individualized vancomycin dosage regimens could be developed for postoperative neurosurgical patients with different CSF albumin levels through model simulations. The CSF albumin level is a determinant of CSF vancomycin concentration.
authors.affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Xingang
authors.initials: X
authors.lastname: Li
authors.affiliation: Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Yuanxing
authors.initials: Y
authors.lastname: Wu
authors.affiliation: College of Pharmacy, Western New England University, Springfield, Massachusetts 01119, USA.
authors.forename: Shusen
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Shenghui
authors.initials: S
authors.lastname: Mei
authors.affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Jiaqing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: ttyywq@hotmail.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: 1022zzg@sina.com.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood* / Q000134:cerebrospinal fluid*; D001812:Blood-Brain Barrier; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011184:Postoperative Period; D014640:Vancomycin / Q000008:administration & dosage / Q000097:blood* / Q000134:cerebrospinal fluid*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: CSF albumin; HPLC; blood-CSF barrier; distribution; individualized therapy; population pharmacokinetics; postoperative neurosurgical patient; simulation; vancomycin