Rudolf Buchheim Award 2026: solanidine as a dietary derived CYP2D6 biomarker.

Area of Science:

• Pharmacology and Toxicology
• Genetics
• Personalized Medicine

Background:

• CYP2D6 is a highly variable drug-metabolizing enzyme affecting ~20% of common drugs.
• Variability in CYP2D6 activity causes interindividual differences in drug pharmacokinetics, potentially leading to adverse events or treatment failure.
• Current CYP2D6 genotyping predicts metabolizer phenotypes but doesn't account for factors like polypharmacy.

Purpose of the Study:

• To investigate the performance and applicability of the novel CYP2D6 biomarker solanidine.
• To assess solanidine's utility in accurate CYP2D6 phenotyping.
• To explore solanidine's potential in elucidating genotype-phenotype mismatches due to polypharmacy.

Main Methods:

• Utilized the novel biomarker solanidine for CYP2D6 phenotyping.
• Analyzed single plasma samples for accurate phenotyping.
• Investigated CYP2D6 phenoconversion in the context of polypharmacy.

Main Results:

• Demonstrated that a single plasma sample is sufficient for accurate CYP2D6 phenotyping using solanidine.
• Showed that solanidine can elucidate CYP2D6 phenoconversion (genotype-phenotype mismatch) caused by polypharmacy.
• Established solanidine as a tool for studying non-genetic variations in CYP2D6 activity.

Conclusions:

• Solanidine enables accurate CYP2D6 phenotyping, improving the understanding of non-genetic variations.
• This biomarker opens new avenues for personalized medicine by addressing polypharmacy's impact on drug metabolism.
• Solanidine phenotyping can optimize patient therapy decisions, enhancing treatment outcomes and safety.