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Assessment of the Effect of Filgotinib on the Pharmacokinetics of Atorvastatin, Pravastatin, and Rosuvastatin in Healthy Adult Participants
Filgotinib, an oral Janus kinase‐1 preferential inhibitor, is approved in Europe and Japan for adults with rheumatoid arthritis. Patients with rheumatoid arthritis are at higher risk of cardiovascular morbidity/mortality; thus, it is important to understand potential drug‐drug interactions of filgot...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293227/ https://www.ncbi.nlm.nih.gov/pubmed/34468080 http://dx.doi.org/10.1002/cpdd.1015 |
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author | Anderson, Kacey Nelson, Cara H. Gong, Qi Alani, Muhsen Tarnowski, Thomas Othman, Ahmed A. |
author_facet | Anderson, Kacey Nelson, Cara H. Gong, Qi Alani, Muhsen Tarnowski, Thomas Othman, Ahmed A. |
author_sort | Anderson, Kacey |
collection | PubMed |
description | Filgotinib, an oral Janus kinase‐1 preferential inhibitor, is approved in Europe and Japan for adults with rheumatoid arthritis. Patients with rheumatoid arthritis are at higher risk of cardiovascular morbidity/mortality; thus, it is important to understand potential drug‐drug interactions of filgotinib with lipid‐lowering agents. This open‐label, randomized, 2‐way crossover study evaluated the pharmacokinetics of atorvastatin, pravastatin, and rosuvastatin with and without filgotinib coadministration. Healthy participants (N = 27) received single doses of atorvastatin (40 mg) and of a pravastatin (40 mg)/rosuvastatin (10 mg) cocktail—alone or with filgotinib (200 mg once daily for 11 days)—on 2 different occasions with washout in between. Serial pharmacokinetic blood samples were collected, and safety was assessed. Pharmacokinetic parameters were evaluated using 90% confidence intervals (CI) of the geometric least‐squares mean (GLSM) ratio of the test treatment (statin coadministration with filgotinib) vs statin alone, with prespecified lack‐of‐interaction bounds of 0.70 to 1.43. Coadministration of filgotinib did not affect atorvastatin area under the plasma concentration–time curve extrapolated to infinity (AUC(inf); [GLSM ratios (90% CI): 0.91 (0.84‐0.99)]), but maximum concentration [C(max)] was slightly lower [0.82 (0.69‐0.99)]. The exposure of 2‐hydroxy‐atorvastatin was unaffected (GLSM ratios [90% CI], 0.98 [0.81‐1.19] for C(max); 1.11 [1.02‐1.22] for AUC(inf)). Pravastatin AUC(inf) was also unaffected (GLSM ratios, 1.22 [1.05‐1.41], but C(max) was slightly higher 1.25 [1.01‐1.54]). Rosuvastatin exposure was moderately higher with filgotinib coadministration—GLSM ratios (90% CI), 1.68 (1.43‐1.97) for C(max); 1.42 (1.30‐1.57) for AUC(inf)—but this was not considered clinically relevant. These results indicate that filgotinib has no clinically meaningful effect on exposure of atorvastatin, pravastatin, or rosuvastatin. |
format | Online Article Text |
id | pubmed-9293227 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92932272022-07-20 Assessment of the Effect of Filgotinib on the Pharmacokinetics of Atorvastatin, Pravastatin, and Rosuvastatin in Healthy Adult Participants Anderson, Kacey Nelson, Cara H. Gong, Qi Alani, Muhsen Tarnowski, Thomas Othman, Ahmed A. Clin Pharmacol Drug Dev Articles Filgotinib, an oral Janus kinase‐1 preferential inhibitor, is approved in Europe and Japan for adults with rheumatoid arthritis. Patients with rheumatoid arthritis are at higher risk of cardiovascular morbidity/mortality; thus, it is important to understand potential drug‐drug interactions of filgotinib with lipid‐lowering agents. This open‐label, randomized, 2‐way crossover study evaluated the pharmacokinetics of atorvastatin, pravastatin, and rosuvastatin with and without filgotinib coadministration. Healthy participants (N = 27) received single doses of atorvastatin (40 mg) and of a pravastatin (40 mg)/rosuvastatin (10 mg) cocktail—alone or with filgotinib (200 mg once daily for 11 days)—on 2 different occasions with washout in between. Serial pharmacokinetic blood samples were collected, and safety was assessed. Pharmacokinetic parameters were evaluated using 90% confidence intervals (CI) of the geometric least‐squares mean (GLSM) ratio of the test treatment (statin coadministration with filgotinib) vs statin alone, with prespecified lack‐of‐interaction bounds of 0.70 to 1.43. Coadministration of filgotinib did not affect atorvastatin area under the plasma concentration–time curve extrapolated to infinity (AUC(inf); [GLSM ratios (90% CI): 0.91 (0.84‐0.99)]), but maximum concentration [C(max)] was slightly lower [0.82 (0.69‐0.99)]. The exposure of 2‐hydroxy‐atorvastatin was unaffected (GLSM ratios [90% CI], 0.98 [0.81‐1.19] for C(max); 1.11 [1.02‐1.22] for AUC(inf)). Pravastatin AUC(inf) was also unaffected (GLSM ratios, 1.22 [1.05‐1.41], but C(max) was slightly higher 1.25 [1.01‐1.54]). Rosuvastatin exposure was moderately higher with filgotinib coadministration—GLSM ratios (90% CI), 1.68 (1.43‐1.97) for C(max); 1.42 (1.30‐1.57) for AUC(inf)—but this was not considered clinically relevant. These results indicate that filgotinib has no clinically meaningful effect on exposure of atorvastatin, pravastatin, or rosuvastatin. John Wiley and Sons Inc. 2021-09-01 2022-02 /pmc/articles/PMC9293227/ /pubmed/34468080 http://dx.doi.org/10.1002/cpdd.1015 Text en © 2021 Gilead Sciences, Inc. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Articles Anderson, Kacey Nelson, Cara H. Gong, Qi Alani, Muhsen Tarnowski, Thomas Othman, Ahmed A. Assessment of the Effect of Filgotinib on the Pharmacokinetics of Atorvastatin, Pravastatin, and Rosuvastatin in Healthy Adult Participants |
title | Assessment of the Effect of Filgotinib on the Pharmacokinetics of Atorvastatin, Pravastatin, and Rosuvastatin in Healthy Adult Participants |
title_full | Assessment of the Effect of Filgotinib on the Pharmacokinetics of Atorvastatin, Pravastatin, and Rosuvastatin in Healthy Adult Participants |
title_fullStr | Assessment of the Effect of Filgotinib on the Pharmacokinetics of Atorvastatin, Pravastatin, and Rosuvastatin in Healthy Adult Participants |
title_full_unstemmed | Assessment of the Effect of Filgotinib on the Pharmacokinetics of Atorvastatin, Pravastatin, and Rosuvastatin in Healthy Adult Participants |
title_short | Assessment of the Effect of Filgotinib on the Pharmacokinetics of Atorvastatin, Pravastatin, and Rosuvastatin in Healthy Adult Participants |
title_sort | assessment of the effect of filgotinib on the pharmacokinetics of atorvastatin, pravastatin, and rosuvastatin in healthy adult participants |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293227/ https://www.ncbi.nlm.nih.gov/pubmed/34468080 http://dx.doi.org/10.1002/cpdd.1015 |
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