Current evidence supporting solanidine and its metabolites as biomarkers of CYP2D6 activity.

Solanidine, a dietary steroidal alkaloid from potatoes, is metabolised by CYP2D6 into 4-hydroxysolanidine and 3,4-seco-solanidine-3,4-dioic acid: the ratio between the parent compound and its metabolites reflects the enzyme activity actually available in vivo, rather than genotype alone.

CYP2D6 genotyping does not capture in vivo enzyme activity, which is strongly modified by environmental and clinical factors causing phenoconversion. This minireview synthesises a decade of work on solanidine, a potato-derived steroidal alkaloid, and its CYP2D6-dependent metabolites — chiefly 4-hydroxysolanidine and 3,4-seco-solanidine-3,4-dioic acid, initially identified through untargeted metabolomics. Poor metabolisers accumulate solanidine and show near-absent metabolites, a pattern reproduced across diverse populations and analytical methods. These biomarkers respond to pharmacological CYP2D6 inhibition, correlate with established probe drugs, and detect both phenoconversion and rare variants missed by genotyping. The authors flag two limitations: variable dietary exposure, and poor discrimination between adjacent phenotypes, particularly intermediate, normal and ultrarapid metabolisers.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Phenoconversion is the main blind spot of prescription pharmacogenetics: a nominally normal metaboliser can behave as a poor one under an inhibitor, and no genotype will reveal it. An endogenous, diet-derived biomarker measurable without a probe drug is therefore a serious avenue for real-time functional phenotyping. Two obstacles remain, which the authors do not hide and which rule out clinical use as it stands: the lack of analytical standardisation and, above all, the inability to separate intermediate, normal and ultrarapid metabolisers — precisely the categories where dose adjustment is decided.

Analysis by Dr Thibaut Benquey