Population Pharmacokinetics and Cerebrospinal Fluid Penetration of Intravenous Vancomycin in Intracranial Hemorrhage Patients with External Ventricular Drains: Implications for Dosing and Therapeutic Drug Monitoring

Yu-Ju Tseng,1,2,* Liang Juan,2,* Chien-Chih Wu,1,2 Yi-Xuan Lan,3 Guan-Yuan Chen,4,5 Abel Po-Hao Huang,6 Kuo-Wei Chen,6 Kuo-Chuan Wang,6 Hui-Tzung Luh,7,8 Shu-Wen Lin2,9,10 1Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; 2School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Department of Medical Research, National Taiwan University, Taipei, Taiwan; 4Forensic and Clinical Toxicology Center, National Taiwan University Hospital, Taipei, Taiwan; 5Department and Graduate Institute of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; 6Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan; 7Medical Department, International SOS Company Limited, Taipei, Taiwan; 8Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan; 9Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; 10Department of Pharmacy, National Taiwan University Cancer Center, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Hui-Tzung Luh, Email john.luh@internationalsos.com Shu-Wen Lin, Email shuwenlin@ntu.edu.twPurpose: Vancomycin is frequently used to treat central nervous system (CNS) infections, yet its cerebrospinal fluid (CSF) penetration remains poorly characterized in patients with intracranial hemorrhage (ICH) requiring external ventricular drains (EVDs).Methods: A prospective observational study was conducted on nine neurosurgical patients with ICH and EVDs receiving intravenous vancomycin. Plasma and CSF samples were collected at predefined time points and analyzed by validated assays. Noncompartmental analysis, regression modeling, and nonlinear mixed-effects pharmacokinetic (PK) modeling were performed.Results: The AUCCSF/plasma ratios ranged from 0.84% to 14.22%. CSF penetration correlated strongly with plasma–CSF concentration ratios at the end of infusion ...