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

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.