Erschienen in:
British Journal of Clinical Pharmacology, 78 (2014) 6, Seite 1185-1200
Sprache:
Englisch
DOI:
10.1111/bcp.12468
ISSN:
0306-5251;
1365-2125
Entstehung:
Anmerkungen:
Beschreibung:
<jats:p>Human radiolabel studies are traditionally conducted to provide a definitive understanding of the human absorption, distribution, metabolism and excretion (<jats:styled-content style="fixed-case">ADME</jats:styled-content>) properties of a drug. However, advances in technology over the past decade have allowed alternative methods to be employed to obtain both clinical <jats:styled-content style="fixed-case">ADME</jats:styled-content> and pharmacokinetic (<jats:styled-content style="fixed-case">PK</jats:styled-content>) information. These include microdose and microtracer approaches using accelerator mass spectrometry, and the identification and quantification of metabolites in samples from classical human <jats:styled-content style="fixed-case">PK</jats:styled-content> 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 <jats:styled-content style="fixed-case">G</jats:styled-content>laxo<jats:styled-content style="fixed-case">S</jats:styled-content>mith<jats:styled-content style="fixed-case">K</jats:styled-content>line. 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 <jats:styled-content style="fixed-case">ADME</jats:styled-content> properties of drug molecules.</jats:p>