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Pharmacokinetic Assessment of Drug‐Drug Interactions of Isavuconazole With the Immunosuppressants Cyclosporine, Mycophenolic Acid, Prednisolone, Sirolimus, and Tacrolimus in Healthy Adults

This report summarizes phase 1 studies that evaluated pharmacokinetic interactions between the novel triazole antifungal agent isavuconazole and the immunosuppressants cyclosporine, mycophenolic acid, prednisolone, sirolimus, and tacrolimus in healthy adults. Healthy subjects received single oral do...

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Autores principales: Groll, Andreas H., Desai, Amit, Han, David, Howieson, Corrie, Kato, Kota, Akhtar, Shahzad, Kowalski, Donna, Lademacher, Christopher, Lewis, William, Pearlman, Helene, Mandarino, Debra, Yamazaki, Takao, Townsend, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5298005/
https://www.ncbi.nlm.nih.gov/pubmed/27273343
http://dx.doi.org/10.1002/cpdd.284
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author Groll, Andreas H.
Desai, Amit
Han, David
Howieson, Corrie
Kato, Kota
Akhtar, Shahzad
Kowalski, Donna
Lademacher, Christopher
Lewis, William
Pearlman, Helene
Mandarino, Debra
Yamazaki, Takao
Townsend, Robert
author_facet Groll, Andreas H.
Desai, Amit
Han, David
Howieson, Corrie
Kato, Kota
Akhtar, Shahzad
Kowalski, Donna
Lademacher, Christopher
Lewis, William
Pearlman, Helene
Mandarino, Debra
Yamazaki, Takao
Townsend, Robert
author_sort Groll, Andreas H.
collection PubMed
description This report summarizes phase 1 studies that evaluated pharmacokinetic interactions between the novel triazole antifungal agent isavuconazole and the immunosuppressants cyclosporine, mycophenolic acid, prednisolone, sirolimus, and tacrolimus in healthy adults. Healthy subjects received single oral doses of cyclosporine (300 mg; n = 24), mycophenolate mofetil (1000 mg; n = 24), prednisone (20 mg; n = 21), sirolimus (2 mg; n = 22), and tacrolimus (5 mg; n = 24) in the presence and absence of clinical doses of oral isavuconazole (200 mg 3 times daily for 2 days; 200 mg once daily thereafter). Coadministration with isavuconazole increased the area under the concentration‐time curves (AUC(0–∞)) of tacrolimus, sirolimus, and cyclosporine by 125%, 84%, and 29%, respectively, and the AUCs of mycophenolic acid and prednisolone by 35% and 8%, respectively. Maximum concentrations (C(max)) of tacrolimus, sirolimus, and cyclosporine were 42%, 65%, and 6% higher, respectively; C(max) of mycophenolic acid and prednisolone were 11% and 4% lower, respectively. Isavuconazole pharmacokinetics were mostly unaffected by the immunosuppressants. Two subjects experienced elevated creatinine levels in the cyclosporine study; most adverse events were not considered to be of clinical concern. These results indicate that isavuconazole is an inhibitor of cyclosporine, mycophenolic acid, sirolimus, and tacrolimus metabolism.
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spelling pubmed-52980052017-02-22 Pharmacokinetic Assessment of Drug‐Drug Interactions of Isavuconazole With the Immunosuppressants Cyclosporine, Mycophenolic Acid, Prednisolone, Sirolimus, and Tacrolimus in Healthy Adults Groll, Andreas H. Desai, Amit Han, David Howieson, Corrie Kato, Kota Akhtar, Shahzad Kowalski, Donna Lademacher, Christopher Lewis, William Pearlman, Helene Mandarino, Debra Yamazaki, Takao Townsend, Robert Clin Pharmacol Drug Dev Articles This report summarizes phase 1 studies that evaluated pharmacokinetic interactions between the novel triazole antifungal agent isavuconazole and the immunosuppressants cyclosporine, mycophenolic acid, prednisolone, sirolimus, and tacrolimus in healthy adults. Healthy subjects received single oral doses of cyclosporine (300 mg; n = 24), mycophenolate mofetil (1000 mg; n = 24), prednisone (20 mg; n = 21), sirolimus (2 mg; n = 22), and tacrolimus (5 mg; n = 24) in the presence and absence of clinical doses of oral isavuconazole (200 mg 3 times daily for 2 days; 200 mg once daily thereafter). Coadministration with isavuconazole increased the area under the concentration‐time curves (AUC(0–∞)) of tacrolimus, sirolimus, and cyclosporine by 125%, 84%, and 29%, respectively, and the AUCs of mycophenolic acid and prednisolone by 35% and 8%, respectively. Maximum concentrations (C(max)) of tacrolimus, sirolimus, and cyclosporine were 42%, 65%, and 6% higher, respectively; C(max) of mycophenolic acid and prednisolone were 11% and 4% lower, respectively. Isavuconazole pharmacokinetics were mostly unaffected by the immunosuppressants. Two subjects experienced elevated creatinine levels in the cyclosporine study; most adverse events were not considered to be of clinical concern. These results indicate that isavuconazole is an inhibitor of cyclosporine, mycophenolic acid, sirolimus, and tacrolimus metabolism. John Wiley and Sons Inc. 2016-07-25 2017 /pmc/articles/PMC5298005/ /pubmed/27273343 http://dx.doi.org/10.1002/cpdd.284 Text en © 2016, The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://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 Articles
Groll, Andreas H.
Desai, Amit
Han, David
Howieson, Corrie
Kato, Kota
Akhtar, Shahzad
Kowalski, Donna
Lademacher, Christopher
Lewis, William
Pearlman, Helene
Mandarino, Debra
Yamazaki, Takao
Townsend, Robert
Pharmacokinetic Assessment of Drug‐Drug Interactions of Isavuconazole With the Immunosuppressants Cyclosporine, Mycophenolic Acid, Prednisolone, Sirolimus, and Tacrolimus in Healthy Adults
title Pharmacokinetic Assessment of Drug‐Drug Interactions of Isavuconazole With the Immunosuppressants Cyclosporine, Mycophenolic Acid, Prednisolone, Sirolimus, and Tacrolimus in Healthy Adults
title_full Pharmacokinetic Assessment of Drug‐Drug Interactions of Isavuconazole With the Immunosuppressants Cyclosporine, Mycophenolic Acid, Prednisolone, Sirolimus, and Tacrolimus in Healthy Adults
title_fullStr Pharmacokinetic Assessment of Drug‐Drug Interactions of Isavuconazole With the Immunosuppressants Cyclosporine, Mycophenolic Acid, Prednisolone, Sirolimus, and Tacrolimus in Healthy Adults
title_full_unstemmed Pharmacokinetic Assessment of Drug‐Drug Interactions of Isavuconazole With the Immunosuppressants Cyclosporine, Mycophenolic Acid, Prednisolone, Sirolimus, and Tacrolimus in Healthy Adults
title_short Pharmacokinetic Assessment of Drug‐Drug Interactions of Isavuconazole With the Immunosuppressants Cyclosporine, Mycophenolic Acid, Prednisolone, Sirolimus, and Tacrolimus in Healthy Adults
title_sort pharmacokinetic assessment of drug‐drug interactions of isavuconazole with the immunosuppressants cyclosporine, mycophenolic acid, prednisolone, sirolimus, and tacrolimus in healthy adults
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5298005/
https://www.ncbi.nlm.nih.gov/pubmed/27273343
http://dx.doi.org/10.1002/cpdd.284
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