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Recommendations on the Use of Multiple Labels in Human Mass Balance Studies. | LitMetric

Recommendations on the Use of Multiple Labels in Human Mass Balance Studies.

Drug Metab Dispos

Janssen R&D, Beerse, Belgium (F.C.); H. Lundbeck A/S, Copenhagen, Denmark (M.G.H.); Eli Lilly and Company, Indianapolis, Indiana (K.C.C.); Pfizer Inc., Groton, Connecticut (D.K.S.); Novartis, Basel, Switzerland (A.D.J.); Biopharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden (M.L.P.); Sosei Heptares, Cambridge, United Kingdom (G.S.); AbbVie, North Chicago, Illinois (D.S.W.); Bayer AG, Wuppertal, Germany (K.G., S.I.S.); The Healthcare Business of Merck KGaA, Darmstadt, Germany (H.S.); Novo Nordisk, Maaloev, Denmark (I.B.); Roche Pharma Research and Early Development, Basel, Switzerland (A.A.R.); Servier, Gif-sur-Yvette, France (G.Da.V.); Boehringer-Ingelheim Pharma GmbH & Co. KG, Biberach, Germany (S.B.); Sanofi, Montpellier, France (P.M.); and GSK Research & Development Ltd., Stevenage (G.C.Y.).

Published: February 2024

AI Article Synopsis

Article Abstract

The administration of radiolabeled drug candidates is considered the gold standard in absorption, distribution, metabolism, and excretion studies for small-molecule drugs since it allows facile and accurate quantification of parent drug, metabolites, and total drug-related material independent of the compound structure. The choice of the position of the radiolabel, typically C or H, is critical to obtain relevant information. Sometimes, a biotransformation reaction may lead to cleavage of a part of the molecule. As a result, only the radiolabeled portion can be followed, and information on the fate of the nonlabeled metabolite may be lost. Synthesis and administration of two or more radiolabeled versions of the parent drug as a mixture or in separate studies may resolve this issue but comes with additional challenges. In this paper, we address the questions that may be considered to help make the right choice whether to use a single or multiple radiolabel approach and discuss the pros and cons of different multiple-labeling strategies that can be taken as well as alternative methods that allow the nonlabeled part of the molecule to be followed. SIGNIFICANCE STATEMENT: Radiolabeled studies are the gold standard in drug metabolism research, but molecules can undergo cleavage with loss of the label. This often results in discussions around potential use of multiple labels, which seem to be occurring with increased frequency since an increasing proportion of the small-molecule drugs are tending towards larger molecular weights. This review provides insight and decision criteria in considering a multiple-label approach as well as pros and cons of different strategies that can be followed.

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Source
http://dx.doi.org/10.1124/dmd.123.001429DOI Listing

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