ABSTRACT
Human CYP2D6 is expressed in the liver, intestine, kidney, and brain and is an important enzyme that metabolizes a number of clinically important drugs (Zhou et al. 2009). There are large interindividual variabilities in the expression and activity of CYP2D6. Changes in the expression and activity of this enzyme may cause altered drug clearance, therapeutic efficacy, risk of adverse drug reactions (ADRs), and unfavorable drug–drug interactions (Hukkanen 2012; Matoulkova et al. 2014; Zanger and Schwab 2013). In adults, differences in CYP expression and attributable metabolism are mainly determined by genetic variability and, to a lesser extent, by enzyme induction because of pharmacotherapy, xenobiotic exposure, or dietary factors (Cascorbi 2003; Fuhr 2000; Ingelman-Sundberg 2005; Ingelman-Sundberg et al. 2007; Lamba et al. 2002). Debrisoquine, sparteine, metoprolol, or dextromethorphan are well-established probe drugs for phenotyping CYP2D6 while tramadol can also be used for this purpose (Frank et al. 2007). The enzymatic activity is reflected by various pharmacokinetic metrics such as the partial clearance of a parent compound to the respective CYP2D6-mediated metabolite or metabolic ratios (MRs). A cocktail approach can be used for the in vivo and in vitro phenotyping studies of CYP2D6 together with other major CYPs (Fuhr et al. 2007; Spaggiari et al. 2014; Tanaka et al. 2003).
