Daptomycin Physiology-Based Pharmacokinetic Modeling to Predict Drug Exposure and Pharmacodynamics in Skin and Bone Tissues
| العنوان: | Daptomycin Physiology-Based Pharmacokinetic Modeling to Predict Drug Exposure and Pharmacodynamics in Skin and Bone Tissues |
|---|---|
| المؤلفون: | Romain Garreau, Damien Montange, Antoine Grillon, François Jehl, Tristan Ferry, Laurent Bourguignon, Sylvain Goutelle |
| المساهمون: | Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Pharmacologie Clinique et Toxicologie [CHRU Besancon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), CHU Strasbourg, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université de Lyon, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Pharmaceutiques et Biologiques (ISPB), Université de Lyon-Université de Lyon, Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE) |
| المصدر: | Clinical Pharmacokinetics Clinical Pharmacokinetics, 2022, 61 (10), pp.1443-1456. ⟨10.1007/s40262-022-01168-5⟩ |
| بيانات النشر: | Springer Science and Business Media LLC, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Pharmacology, MESH: Microbial Sensitivity Tests, MESH: Humans, MESH: Staphylococcal Infections / drug therapy, MESH: Daptomycin / pharmacology, Microbial Sensitivity Tests, Staphylococcal Infections, MESH: Bone and Bones, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bone and Bones, Anti-Bacterial Agents, Daptomycin, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Anti-Bacterial Agents, Humans, Pharmacology (medical), MESH: Staphylococcal Infections / microbiology |
| الوصف: | International audience; Background and objective: Daptomycin has been recommended in the treatment of bone and joint infection. Previous work showed that the approved dosage of daptomycin may be insufficient to achieve optimal exposure in patients with bone and joint infection. However, those studies assumed that bone exposure was similar to steady-state daptomycin-free plasma concentrations. We sought to establish a physiologically based pharmacokinetic (PBPK) model of daptomycin to describe the dynamics of daptomycin disposition in bone and skin tissue.Methods: a PBPK model of daptomycin was built using PK-Sim®. Daptomycin concentrations in plasma and bone were obtained from three previously published studies. Physicochemical drug characteristics, mass balance, anthropometrics, and experimental data were used to build and refine the PBPK model. Internal validation of the PBPK model was performed using the usual diagnostic plots. The final PBPK model was then used to run simulations with doses of 6, 8, 10, and 12 mg/kg/24 h. Pharmacokinetic profiles were simulated in 1.000 subjects and the probabilities of target attainment for the area under the concentration-time curve over the bacterial minimum inhibitory concentration were computed in blood, skin, and bone compartments.Results: the final model showed a good fit of all datasets with an absolute average fold error between 0.5 and 2 for all pharmacokinetic quantities in blood, skin and bone tissues. Results of dosing simulations showed that doses ≥10 mg/kg should be used in the case of bacteremia caused by Staphylococcus aureus with a minimum inhibitory concentration >0.5 mg/L or Enterococcus faecalis with a minimum inhibitory concentration >1 mg/L, while doses ≥12 mg/kg should be used in the case of bone and joint infection or complicated skin infection. When considering a lower minimum inhibitory concentration, doses of 6-8 mg/kg would likely achieve a sufficient success rate. However, in the case of infections caused by E. faecalis with a minimum inhibitory concentration >2 mg/L, a higher dosage and combination therapy would be necessary to maximize efficacy.Conclusions: we developed the first daptomycin PBPK/pharmacodynamic model for bone and joint infection, which confirmed that a higher daptomycin dosage is needed to optimize exposure in bone tissue. However, such higher dosages raise safety concerns. In this setting, therapeutic drug monitoring and model-informed precision dosing appear necessary to ensure the right exposure on an individual basis. |
| تدمد: | 1179-1926 0312-5963 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::75b6f6222362845aad3fe52a40ec065f https://doi.org/10.1007/s40262-022-01168-5 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....75b6f6222362845aad3fe52a40ec065f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 11791926 03125963 |
|---|