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

• Main Authors: Justine Heitzmann (Author), Yann Thoma (Author), Romain Bricca (Author), Marie-Claude Gagnieu (Author), Vincent Leclerc (Author), Sandrine Roux (Author), Anne Conrad (Author), Tristan Ferry (Author), Sylvain Goutelle (Author)
• Format: Book
• Published: MDPI AG, 2022-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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 (AUC_24h < 666 mg.h/L) and 31.9% of patients were overexposed (C_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, <i>p</i> < 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.

Item Description

10.3390/pharmaceutics14010114
1999-4923