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Rethinking, reducing, and refining the classical oral tyramine challenge test of monoamine oxidase (MAO) inhibitors
The oral tyramine challenge evaluates the safety of novel monoamine oxidase (MAO) inhibitors when taken with tyramine‐containing food or drinks. In its current design, it comprises an extensive series of tyramine escalation steps until a blood pressure threshold is met. Due to the high variation in...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10582662/ https://www.ncbi.nlm.nih.gov/pubmed/37596819 http://dx.doi.org/10.1111/cts.13612 |
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author | van Hoogdalem, Ewoud‐Jan Smith, Karen L. Hartstra, Jan Constant, John |
author_facet | van Hoogdalem, Ewoud‐Jan Smith, Karen L. Hartstra, Jan Constant, John |
author_sort | van Hoogdalem, Ewoud‐Jan |
collection | PubMed |
description | The oral tyramine challenge evaluates the safety of novel monoamine oxidase (MAO) inhibitors when taken with tyramine‐containing food or drinks. In its current design, it comprises an extensive series of tyramine escalation steps until a blood pressure threshold is met. Due to the high variation in tyramine bioavailability, and thereby in blood pressure effect, this classical design has various limitations, including safety concerns. Based on data from a previously performed tyramine challenge study, the present study explored a reduced new design that escalates up to 400 mg, and evaluates the dose to a tyramine peak plasma concentration of ≥10 ng/mL, instead of a dose up to 800 mg, and to a blood pressure change of ≥30 mm Hg. Tested by trial simulation, the new design proves more efficient than the classical design in terms of better identifying tyramine sensitivity of test and reference treatments and reducing false‐positive and false‐negative rates in estimating tyramine sensitivity by more than 10‐fold. Since it escalates over a lower tyramine dose range, the new design reduces risk to subjects associated with tyramine‐induced blood pressure excursions, is less demanding for study participants, and is more efficient. By its focus on tyramine bioavailability as the primary concern for novel MAO inhibitors, the new tyramine challenge study provides better answers in a simplified and safer design compared with the classical design in trial simulation, warranting its use in future clinical studies. |
format | Online Article Text |
id | pubmed-10582662 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105826622023-10-19 Rethinking, reducing, and refining the classical oral tyramine challenge test of monoamine oxidase (MAO) inhibitors van Hoogdalem, Ewoud‐Jan Smith, Karen L. Hartstra, Jan Constant, John Clin Transl Sci Research The oral tyramine challenge evaluates the safety of novel monoamine oxidase (MAO) inhibitors when taken with tyramine‐containing food or drinks. In its current design, it comprises an extensive series of tyramine escalation steps until a blood pressure threshold is met. Due to the high variation in tyramine bioavailability, and thereby in blood pressure effect, this classical design has various limitations, including safety concerns. Based on data from a previously performed tyramine challenge study, the present study explored a reduced new design that escalates up to 400 mg, and evaluates the dose to a tyramine peak plasma concentration of ≥10 ng/mL, instead of a dose up to 800 mg, and to a blood pressure change of ≥30 mm Hg. Tested by trial simulation, the new design proves more efficient than the classical design in terms of better identifying tyramine sensitivity of test and reference treatments and reducing false‐positive and false‐negative rates in estimating tyramine sensitivity by more than 10‐fold. Since it escalates over a lower tyramine dose range, the new design reduces risk to subjects associated with tyramine‐induced blood pressure excursions, is less demanding for study participants, and is more efficient. By its focus on tyramine bioavailability as the primary concern for novel MAO inhibitors, the new tyramine challenge study provides better answers in a simplified and safer design compared with the classical design in trial simulation, warranting its use in future clinical studies. John Wiley and Sons Inc. 2023-08-21 /pmc/articles/PMC10582662/ /pubmed/37596819 http://dx.doi.org/10.1111/cts.13612 Text en © 2023 Icon PLC. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research van Hoogdalem, Ewoud‐Jan Smith, Karen L. Hartstra, Jan Constant, John Rethinking, reducing, and refining the classical oral tyramine challenge test of monoamine oxidase (MAO) inhibitors |
title | Rethinking, reducing, and refining the classical oral tyramine challenge test of monoamine oxidase (MAO) inhibitors |
title_full | Rethinking, reducing, and refining the classical oral tyramine challenge test of monoamine oxidase (MAO) inhibitors |
title_fullStr | Rethinking, reducing, and refining the classical oral tyramine challenge test of monoamine oxidase (MAO) inhibitors |
title_full_unstemmed | Rethinking, reducing, and refining the classical oral tyramine challenge test of monoamine oxidase (MAO) inhibitors |
title_short | Rethinking, reducing, and refining the classical oral tyramine challenge test of monoamine oxidase (MAO) inhibitors |
title_sort | rethinking, reducing, and refining the classical oral tyramine challenge test of monoamine oxidase (mao) inhibitors |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10582662/ https://www.ncbi.nlm.nih.gov/pubmed/37596819 http://dx.doi.org/10.1111/cts.13612 |
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