The Current State of Biotransformation Science - Industry Survey of In Vitro and In Vivo Practices, Clinical Translation, and Future Trends.

Autor: Savaryn JP; AbbVie, Quantitative, Translational & ADME Sciences, North Chicago, IL, USA. john.savaryn@abbvie.com., Coe K; J&J, Translational PKPD & Investigational Toxicology, San Diego, CA, USA., Cerny MA; Pfizer, Inc, Groton, CT, USA., Colizza K; GSK, DMPK Disposition and Biotransformation, Collegeville, PA, USA. kevin.x.colizza@gsk.com., Moliner P; Sanofi, Montpellier, France., King L; UCB Biopharma, Dept. of DMPK, Slough, UK., Ma B; Genentech, Inc., Department of Drug Metabolism and Pharmacokinetics, South San Francisco, CA, USA., Atherton J; Incyte Research Institute, Translational Sciences, Wilmington, DE, USA., Auclair A; Boehringer Ingelheim Pharmaceuticals, Inc.,Drug Metabolism and Pharmacokinetics, Ridgefield, CT, USA., Cancilla MT; Merck & Co., Inc., Pharmacokinetics, Dynamics, Metabolism, and Bioanalysis, Rahway, NJ, USA., Eno M; Eisai Inc., Global Drug Metabolism and Pharmacokinetics, Cambridge, MA, USA., Jurva U; AstraZeneca, Drug Metabolism and Pharmacokinetics (DMPK), Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, Gothenburg, Sweden., Yue Q; Gilead Sciences, Inc., Drug Metabolism Dept, Foster City, CA, USA., Zhu SX; Takeda Development Center Americas, Inc., Drug Metabolism and Pharmacokinetics & Modeling, Cambridge, MA, USA., Freiberger E; AbbVie, Quantitative, Translational & ADME Sciences, North Chicago, IL, USA., Zhong G; Amgen, Pharmacokinetics and Drug Metabolism Department, South San Francisco, CA, USA., Barlock B; Blueprint Medicines, Cambridge, MA, USA., Nachtigall J; Merck Healthcare KGaA, Department NCE DMPK, Darmstadt, Germany., Laboureur L; R&D Paris-Saclay Servier Institute, DMPK, Gif-Sur-Yvette, France., Pusalkar S; Servier Bioinnovation, LLC, DMPK, Boston, MA, USA., Guo R; Beigene, DMPK, Department of Biology, Shanghai, China., Niehues M; Bayer AG, In Vitro ADME & Isotope Chemistry, Berlin, Germany., Hauri S; Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche, Basel, Switzerland., Carreras ET; Novartis Pharma AG, Novartis Institute for Biomedical Research, Basel, Switzerland., Maurer C; Merck Healthcare KGaA, Department NCE DMPK, Darmstadt, Germany., Prakash C; DMPK/Clinical Pharmacology, Agios Pharmaceuticals, Cambridge, MA, USA., Jenkins GJ; AbbVie, Quantitative, Translational & ADME Sciences, North Chicago, IL, USA.
Jazyk: angličtina
Zdroj: Pharmaceutical research [Pharm Res] 2024 Nov 04. Date of Electronic Publication: 2024 Nov 04.
DOI: 10.1007/s11095-024-03787-y
Abstrakt: Embedded within the field of drug metabolism and pharmacokinetics (DMPK), biotransformation is a discipline that studies the origins, disposition, and structural identity of metabolites to provide a comprehensive safety assessment, including the assessment of exposure coverage in toxicological species. Spanning discovery and development, metabolite identification (metID) scientists employ various strategies and tools to address stage-specific questions aimed at guiding the maturation of early chemical matter into drug candidates. During this process, the identity of major (and minor) circulating human metabolites is ascertained to comply with the regulatory requirements such as the Metabolites in Safety Testing (MIST) guidance. Through the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), the "Translatability of MetID In Vitro Systems Working Group" was created within the Translational and ADME Sciences Leadership Group. The remit of this group was to objectively determine how accurate commonly employed in vitro systems have been with respect to prediction of circulating human metabolites, both qualitatively and quantitatively. A survey composed of 34 questions was conducted across 26 pharmaceutical companies to obtain a foundational understanding of current metID practices, preclinically and clinically, as well as to provide perspective on how successful these practices have been at predicting circulating human metabolites. The results of this survey are presented as an initial snapshot of current industry-based metID practices, including our perspective on how a harmonized framework for the conduct of in vitro metID studies could be established. Future perspectives from current practices to emerging advances with greater translational capability are also provided.
(© 2024. The Author(s).)
Databáze: MEDLINE
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