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Evaluation de différents descripteurs de poids chez le sujet obèse à l’aide d’un modèle de pharmacocinétique de population - application à la metformine, la morphine et l’imatinib

Abstract : Pharmacokinetic of drugs may be altered by pathophysiological changes associated with obesity: renal function, body compartments, expression of metabolism proteins. Real impact may be difficult to appreciate due to small number of specific studies. What is the best size-descriptor for optimal dosing in obesity remains a question of importance. Impact of different size descriptors was studied for three drugs currently used in diabetology, pain and oncology. Population pharmacokinetic modeling was done using Monolix® software to evaluate different covariates (LBW, TBW, BSA, …). CL/F and Vd/F of metformin, highly hydrophilic drug, increases positively with body weight (n=105). LBW was the best size-descriptor leading to substancial decrease in the between-subject variability BSV. No size-descriptors showed significant impact for morphine (n=31). Ideal body weight is the best size-descriptor for imatinib and its main metabolite (n=54), lipophilic drug. It explains only a small part of BSV and fixed dosing stays justified. Population PK analysis are the most formal assessment of morphological covariates and no single size descriptor can described all variabilities. Results must lead us to more systematic population PK analysis. Confirmation studies comparing different dosing regimens have to be done.
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https://tel.archives-ouvertes.fr/tel-00806110
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Submitted on : Friday, March 29, 2013 - 2:47:12 PM
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Christophe Bardin. Evaluation de différents descripteurs de poids chez le sujet obèse à l’aide d’un modèle de pharmacocinétique de population - application à la metformine, la morphine et l’imatinib. Médecine humaine et pathologie. Université René Descartes - Paris V, 2012. Français. ⟨NNT : 2012PA05P649⟩. ⟨tel-00806110⟩

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