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
Affiliations
Justine Heitzmann
Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, Hôpital Pierre Garraud, Service Pharmaceutique, 136 Rue du Commandant Charcot, 69005 Lyon, France
Yann Thoma
School of Management and Engineering Vaud (HEIG-VD), HES-SO University of Applied Sciences and Arts Western Switzerland, 1400 Yverdon-les-Bains, Switzerland
Romain Bricca
Hôpital Nord-Ouest, Service de Médecine Interne et des Maladies Infectieuses, 69400 Villefranche sur Saône, France
Marie-Claude Gagnieu
Hospices Civils de Lyon, Groupement Hospitalier Sud, Service de Biochimie et Biologie Moléculaire, UM Pharmacologie-Toxicologie, 69310 Pierre-Bénite, France
Vincent Leclerc
Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, Hôpital Pierre Garraud, Service Pharmaceutique, 136 Rue du Commandant Charcot, 69005 Lyon, France
Sandrine Roux
Hospices Civils de Lyon, Groupement Hospitalier Nord, Hôpital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, Centre Interrégional de Référence pour la Prise en Charge des Infections Ostéo-Articulaires Complexes (CRIOAc Lyon), 69004 Lyon, France
Anne Conrad
Hospices Civils de Lyon, Groupement Hospitalier Nord, Hôpital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, Centre Interrégional de Référence pour la Prise en Charge des Infections Ostéo-Articulaires Complexes (CRIOAc Lyon), 69004 Lyon, France
Tristan Ferry
Hospices Civils de Lyon, Groupement Hospitalier Nord, Hôpital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, Centre Interrégional de Référence pour la Prise en Charge des Infections Ostéo-Articulaires Complexes (CRIOAc Lyon), 69004 Lyon, France
Sylvain Goutelle
Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, Hôpital Pierre Garraud, Service Pharmaceutique, 136 Rue du Commandant Charcot, 69005 Lyon, France
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.
