# Population pharmacokinetic model and dosing nomogram for daptomycin in adult patients with serious Gram-positive infections: emphasizing the role of loading doses and renal function-based adjustment

## TL;DR

This study shows that adjusting daptomycin doses based on kidney function, rather than weight, improves treatment effectiveness for serious infections.

## Contribution

The study introduces a new dosing strategy for daptomycin based on renal function using population pharmacokinetic modeling.

## Key findings

- Estimated glomerular filtration rate (eGFR) was the most predictive factor for daptomycin pharmacokinetics.
- eGFR-guided dosing outperformed weight-based dosing in achieving pharmacokinetic/pharmacodynamic targets.
- A loading dose combined with eGFR-adjusted maintenance dosing improved efficacy and safety.

## Abstract

Current recommendations for daptomycin dosing are based on body weight. However, it can be hypothesized that dosing based on renal function may improve the attainment of recommended pharmacokinetic (PK)/pharmacodynamic (PD) targets. The aim of this study was to develop a population pharmacokinetic model of daptomycin and propose an individualized dosing strategy to optimize target attainment. Therapeutic drug monitoring data from adult patients treated with daptomycin at a single center between 2022 and 2025 were analyzed using a nonlinear mixed-effects modeling. Monte Carlo simulations were then employed to identify the optimal dosing strategy that maximizes the probability of attaining the PK/PD target. A total of 143 daptomycin serum concentrations from 31 patients were included in the analysis. Estimated glomerular filtration rate (eGFR) was identified as the most predictive covariate for daptomycin pharmacokinetics. In a patient with an eGFR of 90 mL/min, the estimated volume of distribution and clearance of daptomycin were 11.47 L and 0.69 L/h, respectively. An eGFR-guided dosing nomogram was proposed, and simulation results demonstrated that this approach outperformed conventional weight-based dosing in achieving the PK/PD target. These findings support the use of an initial loading dose and individualized maintenance dosing based on eGFR to improve the efficacy and safety of daptomycin therapy.