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Pharmacokinetics of 1-methyl-L-tryptophan after single and repeated subcutaneous application in a porcine model
Increased activity of the tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO) is associated with immunological and neurological disorders, and inhibition of its enzyme activity could be a therapeutic approach for treatment of these disorders. The aim of the present study was to establis...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Japanese Association for Laboratory Animal Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873483/ https://www.ncbi.nlm.nih.gov/pubmed/26725587 http://dx.doi.org/10.1538/expanim.15-0096 |
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author | Wirthgen, Elisa Kanitz, Ellen Tuchscherer, Margret Tuchscherer, Armin Domanska, Grazyna Weitschies, Werner Seidlitz, Anne Scheuch, Eberhard Otten, Winfried |
author_facet | Wirthgen, Elisa Kanitz, Ellen Tuchscherer, Margret Tuchscherer, Armin Domanska, Grazyna Weitschies, Werner Seidlitz, Anne Scheuch, Eberhard Otten, Winfried |
author_sort | Wirthgen, Elisa |
collection | PubMed |
description | Increased activity of the tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO) is associated with immunological and neurological disorders, and inhibition of its enzyme activity could be a therapeutic approach for treatment of these disorders. The aim of the present study was to establish a large animal model to study the accumulation of the potential IDO inhibitor 1-methyltryptophan (1-MT) in blood and different organs of domestic pigs (Sus scrofa domestica). Because 1-MT has not been previously evaluated in pigs, the pharmacokinetics of a single subcutaneous 1-MT application was investigated. Based on this kinetic study, a profile for repeated 1-MT applications over a period of five days was simulated and tested. The results show that a single administration of 1-MT increases its concentrations in blood, with the maximum concentration being obtained at 12 h. Repeated daily injections of 1‑MT generated increasing plasma concentrations followed by a steady-state after two days. Twelve hours after the final application, accumulation of 1-MT was observed in the brain and other organs, with a substantial variability among various tissues. The concentrations of 1-MT measured in plasma and tissues were similar to, or even higher, than those of tryptophan. Our data indicate that repeated subcutaneous injections of 1-MT provide a suitable model for accumulation of 1-MT in plasma and tissues of domestic pigs. These findings provide a basis for further research on the immunoregulatory functions of IDO in a large animal model. |
format | Online Article Text |
id | pubmed-4873483 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Japanese Association for Laboratory Animal Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-48734832016-05-25 Pharmacokinetics of 1-methyl-L-tryptophan after single and repeated subcutaneous application in a porcine model Wirthgen, Elisa Kanitz, Ellen Tuchscherer, Margret Tuchscherer, Armin Domanska, Grazyna Weitschies, Werner Seidlitz, Anne Scheuch, Eberhard Otten, Winfried Exp Anim Original Increased activity of the tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO) is associated with immunological and neurological disorders, and inhibition of its enzyme activity could be a therapeutic approach for treatment of these disorders. The aim of the present study was to establish a large animal model to study the accumulation of the potential IDO inhibitor 1-methyltryptophan (1-MT) in blood and different organs of domestic pigs (Sus scrofa domestica). Because 1-MT has not been previously evaluated in pigs, the pharmacokinetics of a single subcutaneous 1-MT application was investigated. Based on this kinetic study, a profile for repeated 1-MT applications over a period of five days was simulated and tested. The results show that a single administration of 1-MT increases its concentrations in blood, with the maximum concentration being obtained at 12 h. Repeated daily injections of 1‑MT generated increasing plasma concentrations followed by a steady-state after two days. Twelve hours after the final application, accumulation of 1-MT was observed in the brain and other organs, with a substantial variability among various tissues. The concentrations of 1-MT measured in plasma and tissues were similar to, or even higher, than those of tryptophan. Our data indicate that repeated subcutaneous injections of 1-MT provide a suitable model for accumulation of 1-MT in plasma and tissues of domestic pigs. These findings provide a basis for further research on the immunoregulatory functions of IDO in a large animal model. Japanese Association for Laboratory Animal Science 2015-12-28 2016 /pmc/articles/PMC4873483/ /pubmed/26725587 http://dx.doi.org/10.1538/expanim.15-0096 Text en ©2016 Japanese Association for Laboratory Animal Science http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. |
spellingShingle | Original Wirthgen, Elisa Kanitz, Ellen Tuchscherer, Margret Tuchscherer, Armin Domanska, Grazyna Weitschies, Werner Seidlitz, Anne Scheuch, Eberhard Otten, Winfried Pharmacokinetics of 1-methyl-L-tryptophan after single and repeated subcutaneous application in a porcine model |
title | Pharmacokinetics of 1-methyl-L-tryptophan after single and repeated
subcutaneous application in a porcine model |
title_full | Pharmacokinetics of 1-methyl-L-tryptophan after single and repeated
subcutaneous application in a porcine model |
title_fullStr | Pharmacokinetics of 1-methyl-L-tryptophan after single and repeated
subcutaneous application in a porcine model |
title_full_unstemmed | Pharmacokinetics of 1-methyl-L-tryptophan after single and repeated
subcutaneous application in a porcine model |
title_short | Pharmacokinetics of 1-methyl-L-tryptophan after single and repeated
subcutaneous application in a porcine model |
title_sort | pharmacokinetics of 1-methyl-l-tryptophan after single and repeated
subcutaneous application in a porcine model |
topic | Original |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873483/ https://www.ncbi.nlm.nih.gov/pubmed/26725587 http://dx.doi.org/10.1538/expanim.15-0096 |
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