External Validation of a Pharmacokinetic Model Developed for Vancomycin Administration via Target-Controlled Infusion.

Purpose: Target-controlled infusion (TCI) could provide a patient-tailored approach for vancomycin dosing. This study aimed to externally evaluate the predictive performance of a previously constructed pharmacokinetic model of vancomycin (Choi model) specifically optimized for TCI administration of vancomycin differing from the existing model, and to assess the feasibility of administering vancomycin via TCI in clinical practice. Additionally, clinical outcomes were exploratively compared between the TCI and intermittent infusion (standard) methods for vancomycin administration.

Patients And Methods: Clinically ill patients were randomly assigned in a 1:1 ratio to either the TCI or standard group. In the TCI group, vancomycin was administered using the Choi model, targeting an initial concentration of 25 mg/L, adjusted to maintain therapeutic levels (20-30 mg/L). The standard group received a loading dose of 25 mg/kg, then 15 mg/kg every 12 hours. Vancomycin concentrations for analysis were obtained from three blood samples per patient at set times, along with routine therapeutic drug monitoring data. Predictive performance was assessed using four parameters: inaccuracy, divergence, bias, and wobble. The occurrence of acute kidney injury (AKI) during and up to 7 days after vancomycin was investigated.

Results: The study was terminated early due to challenges in enrolling subjects (TCI: n=12, standard: n=13). Thirty-seven serum concentration measurements from the TCI group were analyzed. Pooled median bias and inaccuracy (95% confidence interval) were -2.7 (-7.3 to 1.9) and 17.0 (13.9 to 20.2), respectively. AKI incidence was similar between groups (TCI: n=0, standard: n=1) in this exploratory analysis, but caution is warranted in interpreting these outcomes as the planned sample size was not met.

Conclusion: The predictive performance of the TCI system integrated with the Choi model was suitable for clinical use. Further studies with a large cohort should be performed to determine the clinical effectiveness of vancomycin administered via the TCI method.

Trial Registration: This study was registered at the Clinical Research Information Service of the Korean National Institute of Health (CRIS, http://cris.nih.go.kr), with registration number KCT0003462, on January 31, 2019).