دورية أكاديمية
A Quantitative Systems Pharmacology Model Describing the Cellular Kinetic-Pharmacodynamic Relationship for a Live Biotherapeutic Product to Support Microbiome Drug Development.
العنوان: | A Quantitative Systems Pharmacology Model Describing the Cellular Kinetic-Pharmacodynamic Relationship for a Live Biotherapeutic Product to Support Microbiome Drug Development. |
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المؤلفون: | Renardy M; Applied BioMath LLC, Concord, Massachusetts, USA., Prokopienko AJ; Takeda Development Center Americas, Inc., Cambridge, Massachusetts, USA., Maxwell JR; Takeda Development Center Americas, Inc., Cambridge, Massachusetts, USA., Flusberg DA; Applied BioMath LLC, Concord, Massachusetts, USA., Makaryan S; Applied BioMath LLC, Concord, Massachusetts, USA., Selimkhanov J; Takeda Development Center Americas, Inc., Cambridge, Massachusetts, USA., Vakilynejad M; Takeda Development Center Americas, Inc., Cambridge, Massachusetts, USA., Subramanian K; Applied BioMath LLC, Concord, Massachusetts, USA., Wille L; Takeda Development Center Americas, Inc., Cambridge, Massachusetts, USA. |
المصدر: | Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2023 Sep; Vol. 114 (3), pp. 633-643. Date of Electronic Publication: 2023 Jun 02. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Wiley Country of Publication: United States NLM ID: 0372741 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-6535 (Electronic) Linking ISSN: 00099236 NLM ISO Abbreviation: Clin Pharmacol Ther Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2015- : Hoboken, NJ : Wiley Original Publication: St. Louis : C.V. Mosby |
مواضيع طبية MeSH: | Vancomycin* , Microbiota*, Humans ; Kinetics ; Network Pharmacology ; Drug Development |
مستخلص: | Live biotherapeutic products (LBPs) are human microbiome therapies showing promise in the clinic for a range of diseases and conditions. Describing the kinetics and behavior of LBPs poses a unique modeling challenge because, unlike traditional therapies, LBPs can expand, contract, and colonize the host digestive tract. Here, we present a novel cellular kinetic-pharmacodynamic quantitative systems pharmacology model of an LBP. The model describes bacterial growth and competition, vancomycin effects, binding and unbinding to the epithelial surface, and production and clearance of butyrate as a therapeutic metabolite. The model is calibrated and validated to published data from healthy volunteers. Using the model, we simulate the impact of treatment dose, frequency, and duration as well as vancomycin pretreatment on butyrate production. This model enables model-informed drug development and can be used for future microbiome therapies to inform decision making around antibiotic pretreatment, dose selection, loading dose, and dosing duration. (© 2023 Takeda Pharmaceuticals. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.) |
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المشرفين على المادة: | 6Q205EH1VU (Vancomycin) |
تواريخ الأحداث: | Date Created: 20230523 Date Completed: 20230821 Latest Revision: 20230826 |
رمز التحديث: | 20240628 |
DOI: | 10.1002/cpt.2952 |
PMID: | 37218407 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1532-6535 |
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DOI: | 10.1002/cpt.2952 |