Pharmacokinetics of Vancomycin in Pediatric Patients Receiving Intermittent Hemodialysis or Hemodiafiltration Headline: Vancomycin pharmacokinetics in children on HD/HDF

Abstract Introduction Vancomycin is a common antibiotic used to treat hemodialysis (HD) or hemodiafiltration (HDF)-related infections in pediatric patients, but optimal dosing remains unknown. This is the first observational study to characterize the pharmacokinetics and evaluate dosing of vancomycin in this population. Methods Eligible patients received IV vancomycin 10 mg/kg/dose post-dialysis followed by a series of serum vancomycin concentrations collected pre-, immediately post-, 1-hour-post-, and 4-hour-post-dialysis. The pharmacokinetic parameters were estimated using one and two compartment models and a nonlinear least-squares algorithm. Results Among 42 vancomycin courses in 16 patients, one compartment model had the best fit for observed data. The net drug removal was 43±13% (39% for HD and 50% for HDF) from an average 3-hour HD/HDF session. The mean elimination constant was 0.28 h-1 (standard deviation (SD): 0.11) during intradialytic period compared to 0.0049h-1 (SD: 0.004) when off dialysis. The mean of volume of distribution was 0.65L/kg (SD: 0.19). Duration of dialysis session and mode of dialysis (HD vs. HDF) were significant predictors of vancomycin pharmacokinetic parameters. Half-life was shorter in HDF compared with HD (2.1 h vs. 3.5 h). Conclusions Based on simulations, an initial vancomycin dose of 10 mg/kg/dose and re-dosing post-dialysis was optimal to achieve vancomycin concentration range of 5-12 mg/L at 4-hour post-dialysis and 24-hour area under the curve over minimum inhibitory concentration ≥400h. Therapeutic drug monitoring is necessary to account for residual variability in vancomycin elimination in pediatric patients receiving HD/HDF.