Population Pharmacokinetics of Vancomycin in Postoperative Neurosurgical Patients and the Application in Dosing Recommendation.
Our previous study indicates that cerebrospinal fluid (CSF) albumin level is a determinant of CSF vancomycin concentration for postoperative neurosurgical patients. We aimed to develop an improved vancomycin population pharmacokinetic model with incorporation of more covariates, and to provide dosing guidance for clinicians. Vancomycin was administered intravenously to 20 patients with external ventricular drains after neurosurgical operation. Blood and CSF were collected and vancomycin concentrations were measured by HPLC. A separate CSF compartment was considered, and was linked to the central compartment by a first-order process (QCSF). The clearance of the CSF compartment (ClCSF) was used to characterize vancomycin elimination from CSF through external ventricular drain. Nonlinear mixed-effects modeling approach was used to develop the model. The CSF albumin level (mg/dL) was the covariate influencing QCSF: QCSF=0.0049+0.000021×(CSF albumin-279). The effect of body weight (BW, kg) was significant on central volume (VC): VC=27.84+0.96×(BW-69). All parameters were estimated with an acceptable precision (relative standard error: RSE% < 30.26). The performance of the final model was acceptable with our previous dataset. A simple to use dosage regimen table was created to guide clinicians with vancomycin dosing. This model incorporates variables of both CSF albumin and BW, which offers improvements to the previous pharmacokinetics model.
Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Precision Medicine Research Center for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Xingang
X
Li
Respiratory and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Yuanxing
Y
Wu
College of Pharmacy, Western New England University, Springfield, Massachusetts 01119.
Shusen
S
Sun
Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Precision Medicine Research Center for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Zhigang
Z
Zhao
Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: ttyywq@163.com.
Qiang
Q
Wang
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures / Q000009:adverse effects*; D011183:Postoperative Complications / Q000188:drug therapy* / Q000378:metabolism*; D014640:Vancomycin / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D014640:Vancomycin
CSF albumin; blood-brain barrier; body weight; cerebrospinal fluid; neurosurgical patient; nonlinear mixed-effects modeling; population pharmacokinetics; vancomycin