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Article Dans Une Revue Pharmaceutics Année : 2022

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

Résumé

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 < 666 mg.h/L) and 31.9% of patients were overexposed (Cmin > 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.
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hal-04626209 , version 1 (15-07-2024)

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Justine Heitzmann, Yann Thoma, Romain Bricca, Marie-Claude Gagnieu, Vincent Leclerc, et al.. Implementation and Comparison of Two Pharmacometric Tools for Model-Based Therapeutic Drug Monitoring and Precision Dosing of Daptomycin. Pharmaceutics, 2022, Innovative Tools for Therapeutic Drug Monitoring, 14 (1), pp.114. ⟨10.3390/pharmaceutics14010114⟩. ⟨hal-04626209⟩
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