Cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of 20-25% of commonly used clinical drugs. Between 5 and 10% of Caucasians are homozygous carriers of variant alleles encoding no CYP2D6 enzyme activity, who are classified as poor metabolizers (PMs). Increased risk of supratherapeutic concentrations and adverse effects of CYP2D6 substrates have been reported in PMs during standard recommended dosing. Recently, semiquantitative measurements of the potato-derived compound solanidine and its CYP2D6-dependent metabolite 4-hydroxysolanidine have been shown to predict CYP2D6 PMs with excellent accuracy. We have therefore implemented these measurements as part of our routine therapeutic drug monitoring practice to provide a recommendation for genotyping. Here we report a case where solanidine and 4-hydroxysolanidine signals in a therapeutic drug monitoring sample indicated CYP2D6 PM status in a patient who had previously been genotyped as CYP2D6 *1/*1 and interpreted as a normal metaboliser. The patient had a history of side effects during use of the CYP2D6 substrates perphenazine and aripiprazole at standard doses. Upon reanalysis with an extended genotyping panel, a rare CYP2D6 genotype (CYP2D6*7/*7) encoding PM status was revealed. The report shows the clinical value and feasibility of analysing solanidine and 4-hydroxysolanidine as part of routine therapeutic drug monitoring to identify patients predicted to be CYP2D6 PMs and who should be selected for genotyping, including patients with rare variants not included in standard genotyping panels. Solanidine and 4-hydroxysolanidine semiquantitation can be used as a complementary tool to genotyping and substantially reduce the number-needed-to-genotype for identification of CYP2D6 PMs in clinical practice.
Keywords: CYP2D6 genotype; solanidine; therapeutic drug monitoring.
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