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Development of In Vitro–In Vivo Correlation for Upadacitinib Extended-Release Tablet Formulation
Upadacitinib is a selective Janus Kinase 1 inhibitor which is being developed for the treatment of several inflammatory diseases including rheumatoid arthritis. Upadacitinib was evaluated in Phase 3 studies as an oral extended-release (ER) formulation administered once daily. The purpose of this stu...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814631/ https://www.ncbi.nlm.nih.gov/pubmed/31654328 http://dx.doi.org/10.1208/s12248-019-0378-y |
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author | Mohamed, Mohamed-Eslam F. Trueman, Sheryl Othman, Ahmed A. Han, Jian-Hwa Ju, Tzuchi R. Marroum, Patrick |
author_facet | Mohamed, Mohamed-Eslam F. Trueman, Sheryl Othman, Ahmed A. Han, Jian-Hwa Ju, Tzuchi R. Marroum, Patrick |
author_sort | Mohamed, Mohamed-Eslam F. |
collection | PubMed |
description | Upadacitinib is a selective Janus Kinase 1 inhibitor which is being developed for the treatment of several inflammatory diseases including rheumatoid arthritis. Upadacitinib was evaluated in Phase 3 studies as an oral extended-release (ER) formulation administered once daily. The purpose of this study was to develop a level A in vitro–in vivo correlation (IVIVC) for upadacitinib ER formulation. The pharmacokinetics of four upadacitinib extended-release formulations with different in vitro release characteristics and an immediate-release capsule formulation of upadacitinib were evaluated in 20 healthy subjects in a single-dose, randomized, crossover study. In vivo pharmacokinetic data and in vitro dissolution data (USP Dissolution Apparatus 1; pH 6.8; 100 rpm) were used to establish a level A IVIVC. Three formulations were used to establish the IVIVC, and the fourth formulation was used for external validation. A non-linear IVIVC best described the relationship between upadacitinib in vitro dissolution and in vivo absorption profiles. The absolute percent prediction errors (%PE) for upadacitinib C(max) and AUC were less than 10% for all three formulations used to establish the IVIVC, as well as for the %PE for the external validation formulation and the overall mean internal validation. Model was cross-validated using the leave-one-out approach; all evaluated cross-validation runs met the regulatory acceptance criteria. A level A IVIVC was successfully developed and validated for upadacitinib ER formulation, which meets the FDA and EMA regulatory validation criteria and can be used as surrogate for in vivo bioequivalence. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1208/s12248-019-0378-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6814631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-68146312019-11-06 Development of In Vitro–In Vivo Correlation for Upadacitinib Extended-Release Tablet Formulation Mohamed, Mohamed-Eslam F. Trueman, Sheryl Othman, Ahmed A. Han, Jian-Hwa Ju, Tzuchi R. Marroum, Patrick AAPS J Research Article Upadacitinib is a selective Janus Kinase 1 inhibitor which is being developed for the treatment of several inflammatory diseases including rheumatoid arthritis. Upadacitinib was evaluated in Phase 3 studies as an oral extended-release (ER) formulation administered once daily. The purpose of this study was to develop a level A in vitro–in vivo correlation (IVIVC) for upadacitinib ER formulation. The pharmacokinetics of four upadacitinib extended-release formulations with different in vitro release characteristics and an immediate-release capsule formulation of upadacitinib were evaluated in 20 healthy subjects in a single-dose, randomized, crossover study. In vivo pharmacokinetic data and in vitro dissolution data (USP Dissolution Apparatus 1; pH 6.8; 100 rpm) were used to establish a level A IVIVC. Three formulations were used to establish the IVIVC, and the fourth formulation was used for external validation. A non-linear IVIVC best described the relationship between upadacitinib in vitro dissolution and in vivo absorption profiles. The absolute percent prediction errors (%PE) for upadacitinib C(max) and AUC were less than 10% for all three formulations used to establish the IVIVC, as well as for the %PE for the external validation formulation and the overall mean internal validation. Model was cross-validated using the leave-one-out approach; all evaluated cross-validation runs met the regulatory acceptance criteria. A level A IVIVC was successfully developed and validated for upadacitinib ER formulation, which meets the FDA and EMA regulatory validation criteria and can be used as surrogate for in vivo bioequivalence. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1208/s12248-019-0378-y) contains supplementary material, which is available to authorized users. Springer International Publishing 2019-10-25 /pmc/articles/PMC6814631/ /pubmed/31654328 http://dx.doi.org/10.1208/s12248-019-0378-y Text en © The Author(s) 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Research Article Mohamed, Mohamed-Eslam F. Trueman, Sheryl Othman, Ahmed A. Han, Jian-Hwa Ju, Tzuchi R. Marroum, Patrick Development of In Vitro–In Vivo Correlation for Upadacitinib Extended-Release Tablet Formulation |
title | Development of In Vitro–In Vivo Correlation for Upadacitinib Extended-Release Tablet Formulation |
title_full | Development of In Vitro–In Vivo Correlation for Upadacitinib Extended-Release Tablet Formulation |
title_fullStr | Development of In Vitro–In Vivo Correlation for Upadacitinib Extended-Release Tablet Formulation |
title_full_unstemmed | Development of In Vitro–In Vivo Correlation for Upadacitinib Extended-Release Tablet Formulation |
title_short | Development of In Vitro–In Vivo Correlation for Upadacitinib Extended-Release Tablet Formulation |
title_sort | development of in vitro–in vivo correlation for upadacitinib extended-release tablet formulation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814631/ https://www.ncbi.nlm.nih.gov/pubmed/31654328 http://dx.doi.org/10.1208/s12248-019-0378-y |
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