Evidence for solanidine as a dietary CYP2D6 biomarker : Significant correlation with risperidone metabolism
© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society..
AIMS: The extensive variability in cytochrome P450 2D6 (CYP2D6) metabolism is mainly caused by genetic polymorphisms. However, there is large, unexplained variability in CYP2D6 metabolism within CYP2D6 genotype subgroups. Solanidine, a dietary compound found in potatoes, is a promising phenotype biomarker predicting individual CYP2D6 metabolism. The aim of this study was to investigate the correlation between solanidine metabolism and the CYP2D6-mediated metabolism of risperidone in patients with known CYP2D6 genotypes.
METHODS: The study included therapeutic drug monitoring (TDM) data from CYP2D6-genotyped patients treated with risperidone. Risperidone and 9-hydroxyrisperidone levels were determined during TDM, and reprocessing of the respective TDM full-scan high-resolution mass spectrometry files was applied for semi-quantitative measurements of solanidine and five metabolites (M402, M414, M416, M440 and M444). Spearman's tests determined the correlations between solanidine metabolic ratios (MRs) and the 9-hydroxyrisperidone-to-risperidone ratio.
RESULTS: A total of 229 patients were included. Highly significant, positive correlationswere observed between all solanidine MRs and the 9-hydroxyrisperidone-to-risperidone ratio (ρ > 0.6, P < .0001). The strongest correlation was observed for the M444-to-solanidine MR in patients with functional CYP2D6 metabolism, i.e., genotype activity scores of 1 and 1.5 (ρ 0.72-0.77, P < .0001).
CONCLUSION: The present study shows strong, positive correlations between solanidine metabolism and CYP2D6-mediated risperidone metabolism. The strong correlation within patients carrying CYP2D6 genotypes encoding functional CYP2D6 metabolism suggests that solanidine metabolism may predict individual CYP2D6 metabolism, and hence potentially improve personalized dosing of drugs metabolized by CYP2D6.
| Errataetall: |
CommentIn: Br J Clin Pharmacol. 2024 Mar;90(3):713-714. - PMID 38212061 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:90 |
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| Enthalten in: |
British journal of clinical pharmacology - 90(2024), 3 vom: 23. März, Seite 740-747 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wollmann, Birgit M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 29.02.2024 Date Revised 05.03.2024 published: Print-Electronic CommentIn: Br J Clin Pharmacol. 2024 Mar;90(3):713-714. - PMID 38212061 Citation Status MEDLINE |
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| doi: |
10.1111/bcp.15721 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM354657399 |
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| 100 | 1 | |a Wollmann, Birgit M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Evidence for solanidine as a dietary CYP2D6 biomarker |b Significant correlation with risperidone metabolism |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Completed 29.02.2024 | ||
| 500 | |a Date Revised 05.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Br J Clin Pharmacol. 2024 Mar;90(3):713-714. - PMID 38212061 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. | ||
| 520 | |a AIMS: The extensive variability in cytochrome P450 2D6 (CYP2D6) metabolism is mainly caused by genetic polymorphisms. However, there is large, unexplained variability in CYP2D6 metabolism within CYP2D6 genotype subgroups. Solanidine, a dietary compound found in potatoes, is a promising phenotype biomarker predicting individual CYP2D6 metabolism. The aim of this study was to investigate the correlation between solanidine metabolism and the CYP2D6-mediated metabolism of risperidone in patients with known CYP2D6 genotypes | ||
| 520 | |a METHODS: The study included therapeutic drug monitoring (TDM) data from CYP2D6-genotyped patients treated with risperidone. Risperidone and 9-hydroxyrisperidone levels were determined during TDM, and reprocessing of the respective TDM full-scan high-resolution mass spectrometry files was applied for semi-quantitative measurements of solanidine and five metabolites (M402, M414, M416, M440 and M444). Spearman's tests determined the correlations between solanidine metabolic ratios (MRs) and the 9-hydroxyrisperidone-to-risperidone ratio | ||
| 520 | |a RESULTS: A total of 229 patients were included. Highly significant, positive correlationswere observed between all solanidine MRs and the 9-hydroxyrisperidone-to-risperidone ratio (ρ > 0.6, P < .0001). The strongest correlation was observed for the M444-to-solanidine MR in patients with functional CYP2D6 metabolism, i.e., genotype activity scores of 1 and 1.5 (ρ 0.72-0.77, P < .0001) | ||
| 520 | |a CONCLUSION: The present study shows strong, positive correlations between solanidine metabolism and CYP2D6-mediated risperidone metabolism. The strong correlation within patients carrying CYP2D6 genotypes encoding functional CYP2D6 metabolism suggests that solanidine metabolism may predict individual CYP2D6 metabolism, and hence potentially improve personalized dosing of drugs metabolized by CYP2D6 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a CYP2D6 | |
| 650 | 4 | |a phenotyping | |
| 650 | 4 | |a precision medicine | |
| 650 | 4 | |a solanidine biomarker | |
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| 650 | 7 | |a Cytochrome P-450 CYP2D6 |2 NLM | |
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| 650 | 7 | |a Paliperidone Palmitate |2 NLM | |
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| 650 | 7 | |a Risperidone |2 NLM | |
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| 650 | 7 | |a solanidine |2 NLM | |
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| 700 | 1 | |a Kringen, Marianne Kristiansen |e verfasserin |4 aut | |
| 700 | 1 | |a Ingelman-Sundberg, Magnus |e verfasserin |4 aut | |
| 700 | 1 | |a Molden, Espen |e verfasserin |4 aut | |
| 700 | 1 | |a Størset, Elisabet |e verfasserin |4 aut | |
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