title: Comparison of the pharmacokinetics of vancomycin in neurosurgical and non-neurosurgical patients.
abstract: Although vancomycin concentrations in neurosurgical patients tend to be lower following standard dosing compared with other patient populations, factors influencing vancomycin pharmacokinetics in neurosurgical patients are poorly understood. In this study, pharmacokinetic (PK) parameters in neurosurgical and non-neurosurgical patients were compared. Furthermore, factors influencing vancomycin PK alterations, including those known to augment renal clearance, were determined. Routine therapeutic drug monitoring data from neurosurgical and non-neurosurgical patients were retrospectively collected. Vancomycin PK parameters were estimated using non-linear mixed-effects modelling (NONMEM v.7.2.0); analyses were performed for the entire population and for neurosurgical patients only. Furthermore, the final models performed a bootstrap, visual predictive check and external validation. A total of 359 serum vancomycin concentration data variables from 132 patients were used to execute the PK modelling. Neurosurgical patient factor, the early phase of treatment, underlying liver cirrhosis, co-administration of a nephrotoxic drug and estimated creatinine clearance influenced vancomycin clearance (CL). However, other factors known to augment renal clearance did not affect vancomycin pharmacokinetics. Vancomycin CL was significantly higher in neurosurgical patients than in controls (0.104 ± 0.036 L/h/kg vs. 0.073 ± 0.042 L/h/kg; P <0.01). Augmented vancomycin CL should be considered when determining vancomycin dosages in neurosurgical patients.
authors.affiliation: Department of Pharmacy, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea.
authors.forename: A Jeong
authors.initials: AJ
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588, Republic of Korea.
authors.forename: Ju-Yeun
authors.initials: JY
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong-si 30019, Republic of Korea.
authors.forename: Soo An
authors.initials: SA
authors.lastname: Choi
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea. Electronic address: wgshin@snu.ac.kr.
authors.forename: Wan Gyoon
authors.initials: WG
authors.lastname: Shin
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016903:Drug Monitoring; D006801:Humans; D008657:Metabolic Clearance Rate; D019635:Neurosurgical Procedures; D012189:Retrospective Studies; D044967:Serum / Q000737:chemistry; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: Augmented renal clearance; Neurosurgical patients; Pharmacokinetics; Vancomycin