CYP2D6 phenotype explains reported yohimbine concentrations in four severe acute intoxications / Anna Mueller-Schoell, Robin Michelet, Ferdinand Weinelt, Charlotte Kloft, Gerd Mikus
The indole alkaloid yohimbine is an alpha-2 receptor antagonist used for its sympathomimetic effects. Several cases of yohimbine intoxication have been reported and the most recent one involved four individuals taking a yohimbine-containing drug powder. All individuals developed severe intoxication symptoms and were admitted to the hospital. Even though all individuals were assumed to have taken the same dose of the drug powder, toxicology analyses revealed yohimbine blood concentrations of 249-5631 ng/mL, amounting to a 22-fold difference. The reason for this high variability remained to be elucidated. We used recently reported knowledge on the metabolism of yohimbine together with state-of-the art nonlinear mixed-effects modelling and simulation and show that a patient’s cytochrome P450 2D6 (CYP2D6) phenotype can explain the large differences observed in the measured concentration after intake of the same yohimbine dose. Our findings can be used both for the identification of safe doses in therapeutic use of yohimbine and for an explanation of individual cases of overdosing..
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
24 May 2021 2021 |
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Erschienen: |
24 May 2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:95 |
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Enthalten in: |
Archives of toxicology - 95(2021), 8, Seite 2867-2870 |
Sprache: |
Englisch |
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Weiterer Titel: |
CYP 2D6 phenotype explains reported yohimbine concentrations in four severe acute intoxications |
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Beteiligte Personen: |
McLaughlin, Anna Margarete, 1993- [VerfasserIn] |
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Links: |
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Anmerkungen: |
Gesehen am 11.09.2023 |
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Umfang: |
4 |
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doi: |
10.1007/s00204-021-03082-4 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
185925294X |
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245 | 1 | 0 | |a CYP2D6 phenotype explains reported yohimbine concentrations in four severe acute intoxications |c Anna Mueller-Schoell, Robin Michelet, Ferdinand Weinelt, Charlotte Kloft, Gerd Mikus |
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520 | |a The indole alkaloid yohimbine is an alpha-2 receptor antagonist used for its sympathomimetic effects. Several cases of yohimbine intoxication have been reported and the most recent one involved four individuals taking a yohimbine-containing drug powder. All individuals developed severe intoxication symptoms and were admitted to the hospital. Even though all individuals were assumed to have taken the same dose of the drug powder, toxicology analyses revealed yohimbine blood concentrations of 249-5631 ng/mL, amounting to a 22-fold difference. The reason for this high variability remained to be elucidated. We used recently reported knowledge on the metabolism of yohimbine together with state-of-the art nonlinear mixed-effects modelling and simulation and show that a patient’s cytochrome P450 2D6 (CYP2D6) phenotype can explain the large differences observed in the measured concentration after intake of the same yohimbine dose. Our findings can be used both for the identification of safe doses in therapeutic use of yohimbine and for an explanation of individual cases of overdosing. | ||
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