Optimising Therapeutic Target Attainment in Vancomycin Therapy for Patients Requiring Intermittent Haemodialysis
Danny Tsai, María Patricia Hernández‐Mitre, Amy Legg, Jacqueline Martin, Cherian Sajiv, Sachin Kodgire, William Naughton, Sonja Janson, Jaquelyne T. Hughes, Xin Liu, Jason A. RobertsABSTRACT
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.