دورية أكاديمية
Vinblastine pharmacokinetics in mouse, dog, and human in the context of a physiologically based model incorporating tissue-specific drug binding, transport, and metabolism.
العنوان: | Vinblastine pharmacokinetics in mouse, dog, and human in the context of a physiologically based model incorporating tissue-specific drug binding, transport, and metabolism. |
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المؤلفون: | Witta S; Flint Animal Cancer Center, Colorado State University, Fort Collins, Colorado, USA.; School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado, USA., Collins KP; Flint Animal Cancer Center, Colorado State University, Fort Collins, Colorado, USA.; School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado, USA., Ramirez DA; Flint Animal Cancer Center, Colorado State University, Fort Collins, Colorado, USA., Mannheimer JD; Flint Animal Cancer Center, Colorado State University, Fort Collins, Colorado, USA.; School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado, USA., Wittenburg LA; Department of Surgical and Radiological Sciences, University of California, Davis, California, USA.; University of California, Davis Comprehensive Cancer Center, Sacramento, California, USA., Gustafson DL; Flint Animal Cancer Center, Colorado State University, Fort Collins, Colorado, USA.; School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado, USA.; Developmental Therapeutics Program, University of Colorado Cancer Center, Aurora, Colorado, USA.; Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado, USA. |
المصدر: | Pharmacology research & perspectives [Pharmacol Res Perspect] 2023 Feb; Vol. 11 (1), pp. e01052. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics Country of Publication: United States NLM ID: 101626369 Publication Model: Print Cited Medium: Internet ISSN: 2052-1707 (Electronic) Linking ISSN: 20521707 NLM ISO Abbreviation: Pharmacol Res Perspect Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Hoboken, NJ] : John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics, [2013]- |
مواضيع طبية MeSH: | Vinblastine*/pharmacokinetics , Antineoplastic Agents*/pharmacokinetics, Humans ; Dogs ; Mice ; Animals ; Cytochrome P-450 CYP3A/genetics ; Drug Interactions ; Biological Transport |
مستخلص: | Vinblastine (VBL) is a vinca alkaloid-class cytotoxic chemotherapeutic that causes microtubule disruption and is typically used to treat hematologic malignancies. VBL is characterized by a narrow therapeutic index, with key dose-limiting toxicities being myelosuppression and neurotoxicity. Pharmacokinetics (PK) of VBL is primarily driven by ABCB1-mediated efflux and CYP3A4 metabolism, creating potential for drug-drug interaction. To characterize sources of variability in VBL PK, we developed a physiologically based pharmacokinetic (PBPK) model in Mdr1a/b(-/-) knockout and wild-type mice by incorporating key drivers of PK, including ABCB1 efflux, CYP3A4 metabolism, and tissue-specific tubulin binding, and scaled this model to accurately simulate VBL PK in humans and pet dogs. To investigate the capability of the model to capture interindividual variability in clinical data, virtual populations of humans and pet dogs were generated through Monte Carlo simulation of physiologic and biochemical parameters and compared to the clinical PK data. This model provides a foundation for predictive modeling of VBL PK. The base PBPK model can be further improved with supplemental experimental data identifying drug-drug interactions, ABCB1 polymorphisms and expression, and other sources of physiologic or metabolic variability. (© 2023 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.) |
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معلومات مُعتمدة: | K01 OD026526 United States OD NIH HHS; P30 CA046934 United States CA NCI NIH HHS |
فهرسة مساهمة: | Keywords: comparative oncology; physiologically-based pharmacokinetic modeling (PBPK); vinblastine |
المشرفين على المادة: | 5V9KLZ54CY (Vinblastine) EC 1.14.14.1 (Cytochrome P-450 CYP3A) 0 (Antineoplastic Agents) |
تواريخ الأحداث: | Date Created: 20230112 Date Completed: 20230113 Latest Revision: 20231106 |
رمز التحديث: | 20231106 |
مُعرف محوري في PubMed: | PMC9834611 |
DOI: | 10.1002/prp2.1052 |
PMID: | 36631976 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2052-1707 |
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DOI: | 10.1002/prp2.1052 |