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Clinical Pharmacokinetics and Pharmacodynamics of Roxadustat
The pharmacokinetics of roxadustat are well characterized, with an apparent volume of distribution after oral administration of 22–57 L, apparent clearance of 1.2–2.65 L/h, and renal clearance of 0.030–0.026 L/h in healthy volunteers; the elimination half-life is 9.6–16 h. Plasma binding is 99% and...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891203/ https://www.ncbi.nlm.nih.gov/pubmed/34905154 http://dx.doi.org/10.1007/s40262-021-01095-x |
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author | Czock, David Keller, Frieder |
author_facet | Czock, David Keller, Frieder |
author_sort | Czock, David |
collection | PubMed |
description | The pharmacokinetics of roxadustat are well characterized, with an apparent volume of distribution after oral administration of 22–57 L, apparent clearance of 1.2–2.65 L/h, and renal clearance of 0.030–0.026 L/h in healthy volunteers; the elimination half-life is 9.6–16 h. Plasma binding is 99% and the fraction eliminated by hemodialysis is 2.34%. As an interpretation of the pharmacodynamics of roxadustat, we proposed a concept with a hypothetical cascade of two subsequent effects, first on erythropoetin (EPO) and second on hemoglobin (delta Hb). The primary effect on EPO is observed within a few hours after roxadustat administration and can be modeled using the sigmoidal Hill equation. The concentration at half-maximum effect can be inferred at 10–36 µg/mL, the Hill coefficient at 3.3, and the effect bisection time at 10–17 h, corresponding to EPO half-life. The subsequent effect on hemoglobin (delta Hb) is observed after several weeks and can be interpreted as an irreversible, dose proportional, unsaturable effect, continuing in agreement with the lifespan of red blood cells of 63–112 days. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40262-021-01095-x. |
format | Online Article Text |
id | pubmed-8891203 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-88912032022-03-08 Clinical Pharmacokinetics and Pharmacodynamics of Roxadustat Czock, David Keller, Frieder Clin Pharmacokinet Review Article The pharmacokinetics of roxadustat are well characterized, with an apparent volume of distribution after oral administration of 22–57 L, apparent clearance of 1.2–2.65 L/h, and renal clearance of 0.030–0.026 L/h in healthy volunteers; the elimination half-life is 9.6–16 h. Plasma binding is 99% and the fraction eliminated by hemodialysis is 2.34%. As an interpretation of the pharmacodynamics of roxadustat, we proposed a concept with a hypothetical cascade of two subsequent effects, first on erythropoetin (EPO) and second on hemoglobin (delta Hb). The primary effect on EPO is observed within a few hours after roxadustat administration and can be modeled using the sigmoidal Hill equation. The concentration at half-maximum effect can be inferred at 10–36 µg/mL, the Hill coefficient at 3.3, and the effect bisection time at 10–17 h, corresponding to EPO half-life. The subsequent effect on hemoglobin (delta Hb) is observed after several weeks and can be interpreted as an irreversible, dose proportional, unsaturable effect, continuing in agreement with the lifespan of red blood cells of 63–112 days. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40262-021-01095-x. Springer International Publishing 2021-12-14 2022 /pmc/articles/PMC8891203/ /pubmed/34905154 http://dx.doi.org/10.1007/s40262-021-01095-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Review Article Czock, David Keller, Frieder Clinical Pharmacokinetics and Pharmacodynamics of Roxadustat |
title | Clinical Pharmacokinetics and Pharmacodynamics of Roxadustat |
title_full | Clinical Pharmacokinetics and Pharmacodynamics of Roxadustat |
title_fullStr | Clinical Pharmacokinetics and Pharmacodynamics of Roxadustat |
title_full_unstemmed | Clinical Pharmacokinetics and Pharmacodynamics of Roxadustat |
title_short | Clinical Pharmacokinetics and Pharmacodynamics of Roxadustat |
title_sort | clinical pharmacokinetics and pharmacodynamics of roxadustat |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891203/ https://www.ncbi.nlm.nih.gov/pubmed/34905154 http://dx.doi.org/10.1007/s40262-021-01095-x |
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