Vancomycin dosing nomogram optimized for intermittent hemodialysis patients based on weight and dialysis interval

Optimizing vancomycin therapy in patients with end-stage renal disease (ESRD) requiring intermittent hemodialysis (iHD) is challenging due to its narrow therapeutic index and variable clearance during dialysis. Current dosing strategies often lead to sub-therapeutic or toxic concentrations, risking treatment failure or adverse events like acute kidney injury (AKI). Achieving target pre-iHD trough concentrations, typically 15-20 mg/L, is crucial for efficacy, but individual pharmacokinetic variability necessitates personalized approaches beyond standard protocols. This study addresses the gap by developing a data-driven dosing nomogram.

A retrospective population pharmacokinetic study analyzed 302 vancomycin concentrations from 80 courses across 58 adult patients (45 female, median age 52 years) receiving post-iHD vancomycin therapy. Patients had ≥3 months of iHD and ≥1 recorded vancomycin concentration. Pharmacokinetic analysis was performed using Monolix to develop a one-compartment model. The probability of pharmacokinetic/pharmacodynamic target attainment (PTA) for pre-iHD trough concentrations of 15-20 mg/L was simulated for various vancomycin loading and maintenance doses to guide optimized three-times-weekly post-iHD regimens.

A one-compartment model adequately described the vancomycin data, with actual body weight identified as the sole significant covariate influencing pharmacokinetics. The estimated vancomycin clearance during non-iHD periods was 0.54 L/h, while during iHD periods, it significantly increased to 4.84 L/h. The volume of distribution was estimated at 87.02 L. Simulations strongly supported the use of weight-based loading doses for optimal target attainment. The time to the next iHD session also significantly influenced the PTA of these loading doses, indicating the importance of timing. Interestingly, subjects with higher body weight required relatively lower weight-based doses to achieve targets, and vice versa, suggesting a non-linear relationship. For maintenance doses, the PTA was primarily associated with the pre-iHD trough concentrations and the specific dosing intervals, with weight having a limited impact on maintenance dose PTA. This comprehensive analysis led to the proposal of a new dosing nomogram. > The estimated vancomycin clearance during non-iHD periods was 0.54 L/h, increasing significantly to 4.84 L/h during iHD periods, with a volume of distribution of 87.02 L.