Meeting the MIST regulations: Human metabolism in Phase I using AMS and a tiered bioanalytical approach

Lappin, Graham, Seymour, Mark, Gross, Gerhard , Jorrgensen, Martin, Kall, Morten and Kvaerno, L.isbet (2012) Meeting the MIST regulations: Human metabolism in Phase I using AMS and a tiered bioanalytical approach. Bioanalysis, 4 (4). pp. 407-416. ISSN 1757-6180

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Item Type:Article
Item Status:Live Archive

Abstract

The metabolites in safety testing and ICH-M3 guidance documents emphasize the importance of metabolites when considering safety aspects for new drugs. Both guidances state that relevant metabolites should have safety coverage in humans (although the guidelines have different definitions of relevant metabolites). Not having safety coverage for important metabolites in humans may cause significant delay in the overall pharmaceutical development program. This article discusses the regulatory background regarding safety and metabolites, as well as outlines an integrated strategy taken by one pharmaceutical company, Lundbeck A/S. Lundbeck uses metabolite exposure data from first-in-man studies, obtained using an accelerator MS approach followed by a two-tiered bioanalytical investigation. This enables early availability of key data on this aspect and, overall, represents a powerful risk mitigation strategy. © 2012 Future Science Ltd.

Keywords:carbon 14, radioisotope, analytic method, area under the curve, dosimetry, drug absorption, drug excretion, drug industry, drug metabolism, drug research, high performance liquid chromatography, human, isotope labeling, mass spectrometry, nonhuman, process development, proton nuclear magnetic resonance, quality control, review, Area Under Curve, Biological Availability, Biotransformation, Carbon Radioisotopes, Chromatography, High Pressure Liquid, Clinical Trials, Phase I as Topic, Drug Evaluation, Preclinical, Drug Toxicity, Drugs, Investigational, Humans, Practice Guidelines as Topic
Divisions:College of Science > School of Pharmacy
ID Code:8208
Deposited On:21 Mar 2013 17:07

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