Nonradiolabeled Reaction Phenotyping

For the purposes of definition, nonradiolabeled reaction phenotyping is that conducted ahead of data from radiolabel studies in humans, and is typically conducted before first dosing of humans (Williams et ah, 2003). This differs from reaction phenotyping later in development, which in the presence of radiolabel or metabolite standards is more definitive in nature (Bjornsson et ah, 

Early reaction phenotyping may employ one or more of the independent approaches described in Fig. 15.1, whereas late (definitive) reaction phenotyping is likely to use all three. Early reaction phenotyping has been covered previously (Williams et ah, 2004, 2005), and the essential elements will be presented in the following sections, with relevant updates. 

Compounds that appear to be substrates of other enzyme systems or families, such as UGTs (Williams et ah, 2004), or esterases are less likely to be of concerns to safety in patients, and therefore would not necessarily justify in depth phenotyping of the individual enzymes, especially in the early stages. 

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