Pharmaceutics (Jan 2022)

Implementation and Comparison of Two Pharmacometric Tools for Model-Based Therapeutic Drug Monitoring and Precision Dosing of Daptomycin

  • Justine Heitzmann,
  • Yann Thoma,
  • Romain Bricca,
  • Marie-Claude Gagnieu,
  • Vincent Leclerc,
  • Sandrine Roux,
  • Anne Conrad,
  • Tristan Ferry,
  • Sylvain Goutelle

DOI
https://doi.org/10.3390/pharmaceutics14010114
Journal volume & issue
Vol. 14, no. 1
p. 114

Abstract

Read online

Daptomycin is a candidate for therapeutic drug monitoring (TDM). The objectives of this work were to implement and compare two pharmacometric tools for daptomycin TDM and precision dosing. A nonparametric population PK model developed from patients with bone and joint infection was implemented into the BestDose software. A published parametric model was imported into Tucuxi. We compared the performance of the two models in a validation dataset based on mean error (ME) and mean absolute percent error (MAPE) of individual predictions, estimated exposure and predicted doses necessary to achieve daptomycin efficacy and safety PK/PD targets. The BestDose model described the data very well in the learning dataset. In the validation dataset (94 patients, 264 concentrations), 21.3% of patients were underexposed (AUC24h min > 24.3 mg/L) on the first TDM occasion. The BestDose model performed slightly better than the model in Tucuxi (ME = −0.13 ± 5.16 vs. −1.90 ± 6.99 mg/L, p < 0.001), but overall results were in agreement between the two models. A significant proportion of patients exhibited underexposure or overexposure to daptomycin after the initial dosage, which supports TDM. The two models may be useful for model-informed precision dosing.

Keywords