AIMS: To describe the pharmacokinetics of vancomycin in patients requiring intermittent haemodialysis (iHD) and provide guidance for optimised dosing for a three-times-weekly post-iHD regimen.
METHODS: A population pharmacokinetic study using retrospectively collected data was conducted in a remote Australian dialysis centre. Adult patients receiving post-iHD vancomycin therapy between 1st January 2017 and 31st July 2023 were screened.
INCLUSION CRITERIA: ≥ 3 months of iHD, prescribed vancomycin, and recorded ≥ 1 vancomycin concentration. Pharmacokinetic analysis was performed using Monolix. The probability of pharmacokinetic/pharmacodynamic target attainment (PTA) for pre-iHD trough concentrations of 15-20 mg/L was simulated for various loading and maintenance doses.
RESULTS: A total of 302 vancomycin concentrations were available from 80 courses (58 patients, 45 were female) with a median age of 52 (IQR 45-61) years and weight of 75 (66.5-85.5) kg. A one-compartment model adequately described the data. Actual body weight was the only covariate retained in the final model. The estimated vancomycin clearance during non-iHD periods, during iHD periods, and volume of distribution were 0.54 L/h, 4.84 L/h, and 87.02 L, respectively. The simulations supported weight-based loading doses. The time to the next iHD session also significantly influenced the PTA of loading doses. Subjects with higher weight required lower weight-based doses, and vice versa. The PTA of maintenance doses was associated with the pre-iHD trough concentrations and the dosing intervals. Weight had a limited impact on the PTA of maintenance doses.
CONCLUSION: A comprehensive vancomycin dosing nomogram was suggested for patients requiring iHD. Validation in future prospective studies is recommended.