Human absorption, distribution, metabolism and excretion properties of drug molecules: a plethora of approaches.

Autor: Beaumont C; Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Park Road, Ware, Hertfordshire, SG12 0DP, UK., Young GC, Cavalier T, Young MA
Jazyk: angličtina
Zdroj: British journal of clinical pharmacology [Br J Clin Pharmacol] 2014 Dec; Vol. 78 (6), pp. 1185-200.
DOI: 10.1111/bcp.12468
Abstrakt: Human radiolabel studies are traditionally conducted to provide a definitive understanding of the human absorption, distribution, metabolism and excretion (ADME) properties of a drug. However, advances in technology over the past decade have allowed alternative methods to be employed to obtain both clinical ADME and pharmacokinetic (PK) information. These include microdose and microtracer approaches using accelerator mass spectrometry, and the identification and quantification of metabolites in samples from classical human PK studies using technologies suitable for non-radiolabelled drug molecules, namely liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. These recently developed approaches are described here together with relevant examples primarily from experiences gained in support of drug development projects at GlaxoSmithKline. The advantages of these study designs together with their limitations are described. We also discuss special considerations which should be made for a successful outcome to these new approaches and also to the more traditional human radiolabel study in order to maximize knowledge around the human ADME properties of drug molecules.
(© 2014 The British Pharmacological Society.)
Databáze: MEDLINE
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