Solanidine metabolic ratios for CYP2D6 phenotyping after a standardized potato meal.

INTRODUCTION

The recent identification of the diet-derived CYP2D6 biomarker solanidine, a potato constituent, enables the study of CYP2D6 activity in vivo. Although solanidine metabolic ratios (MR) were shown to be relatively stable over the day with high positive correlations to CYP2D6 phenotype and genotype, the influence of a solanidine-containing potato meal on solanidine metabolite plasma concentrations and MR is unclear.

METHODS

In this study with 20 healthy participants, not preselected for specific CYP2D6 genotypes, a standardized potato meal was administered after 3 days of potato-fasting (DRKS00031441). Blood sampling was conducted at 0, 0.5, 1, 1.5, 2, 3, 4, 5 and 29 h. Participants were genotyped for CYP2D6 and plasma concentrations of solanidine and its metabolites 4-OH-solanidine and 3,4-secosolanidine-3,4-dioic acid (SSDA) were measured by LC-MS/MS. MRs were formed by dividing metabolite by substrate concentrations at each sampling time point.

RESULTS

Solanidine and metabolite plasma concentrations showed no consistent increases. Solanidine plasma concentrations (29 h vs. baseline) increased in median 0.09 ng/mL (range: -0.37 to 1.43 ng/mL). Within the period of 29 h, the linear relationship of solanidine ln MRs to the CYP2D6 activity score (AS) improved over time after intake of the potato meal with the best association after 29 h (r2 = 0.56).

DISCUSSION: Changes in solanidine and metabolite plasma concentrations after the potato meal were variable, which could be attributed to interindividual absorption variability. CYP2D6 phenotyping may be improved by a previous potato meal at least 1 day before blood sampling. This may allow solanidine CYP2D6 phenotyping in populations with low dietary potato consumption.