Comparison of the pharmacokinetics of vancomycin in neurosurgical and non-neurosurgical patients

• Neurosurgical patients have augmented vancomycin clearance (CL).
• The early phase of treatment and underlying liver cirrhosis influence vancomycin CL.
• Co-administration of nephrotoxic drugs decreases vancomycin CL, as expected.
• Other factors known to augment renal clearance did not affect vancomycin CL.

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.