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Population pharmacokinetics of letermovir following oral and intravenous administration in healthy participants and allogeneic hematopoietic cell transplantation recipients
Letermovir is indicated for prophylaxis of cytomegalovirus infection and disease in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Two‐stage population pharmacokinetic (PK) modeling of letermovir was conducted to support dose rationale and evaluate the impact of intrinsic/extrinsic...
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/PMC7965833/ https://www.ncbi.nlm.nih.gov/pubmed/33440077 http://dx.doi.org/10.1002/psp4.12593 |
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author | Prohn, Marita Viberg, Anders Zhang, Da Dykstra, Kevin Davis, Casey Macha, Sreeraj Sabato, Philip de Alwis, Dinesh Iwamoto, Marian Fancourt, Craig Cho, Carolyn R. |
author_facet | Prohn, Marita Viberg, Anders Zhang, Da Dykstra, Kevin Davis, Casey Macha, Sreeraj Sabato, Philip de Alwis, Dinesh Iwamoto, Marian Fancourt, Craig Cho, Carolyn R. |
author_sort | Prohn, Marita |
collection | PubMed |
description | Letermovir is indicated for prophylaxis of cytomegalovirus infection and disease in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Two‐stage population pharmacokinetic (PK) modeling of letermovir was conducted to support dose rationale and evaluate the impact of intrinsic/extrinsic factors. Data from healthy phase I study participants over a wide dose range were modeled to evaluate the effects of selected intrinsic factors, including pharmacogenomics; next, phase III HSCT‐recipient data at steady‐state following clinical doses were modeled. The model in HSCT recipients adequately described letermovir PK following both oral or i.v. administration, and was consistent with the healthy participant model at steady‐state clinical doses. Intrinsic factor effects were not clinically meaningful. These staged analyses indicate that letermovir PK in HSCT recipients and healthy participants differ only with respect to bioavailability and absorption rate. The HSCT recipient model was suitable for predicting exposure for exposure–response analysis supporting final dose selection. |
format | Online Article Text |
id | pubmed-7965833 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79658332021-03-19 Population pharmacokinetics of letermovir following oral and intravenous administration in healthy participants and allogeneic hematopoietic cell transplantation recipients Prohn, Marita Viberg, Anders Zhang, Da Dykstra, Kevin Davis, Casey Macha, Sreeraj Sabato, Philip de Alwis, Dinesh Iwamoto, Marian Fancourt, Craig Cho, Carolyn R. CPT Pharmacometrics Syst Pharmacol Research Letermovir is indicated for prophylaxis of cytomegalovirus infection and disease in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Two‐stage population pharmacokinetic (PK) modeling of letermovir was conducted to support dose rationale and evaluate the impact of intrinsic/extrinsic factors. Data from healthy phase I study participants over a wide dose range were modeled to evaluate the effects of selected intrinsic factors, including pharmacogenomics; next, phase III HSCT‐recipient data at steady‐state following clinical doses were modeled. The model in HSCT recipients adequately described letermovir PK following both oral or i.v. administration, and was consistent with the healthy participant model at steady‐state clinical doses. Intrinsic factor effects were not clinically meaningful. These staged analyses indicate that letermovir PK in HSCT recipients and healthy participants differ only with respect to bioavailability and absorption rate. The HSCT recipient model was suitable for predicting exposure for exposure–response analysis supporting final dose selection. John Wiley and Sons Inc. 2021-03-12 2021-03 /pmc/articles/PMC7965833/ /pubmed/33440077 http://dx.doi.org/10.1002/psp4.12593 Text en © 2021 Merck Sharp & Dohme Corp. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the 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 | Research Prohn, Marita Viberg, Anders Zhang, Da Dykstra, Kevin Davis, Casey Macha, Sreeraj Sabato, Philip de Alwis, Dinesh Iwamoto, Marian Fancourt, Craig Cho, Carolyn R. Population pharmacokinetics of letermovir following oral and intravenous administration in healthy participants and allogeneic hematopoietic cell transplantation recipients |
title | Population pharmacokinetics of letermovir following oral and intravenous administration in healthy participants and allogeneic hematopoietic cell transplantation recipients |
title_full | Population pharmacokinetics of letermovir following oral and intravenous administration in healthy participants and allogeneic hematopoietic cell transplantation recipients |
title_fullStr | Population pharmacokinetics of letermovir following oral and intravenous administration in healthy participants and allogeneic hematopoietic cell transplantation recipients |
title_full_unstemmed | Population pharmacokinetics of letermovir following oral and intravenous administration in healthy participants and allogeneic hematopoietic cell transplantation recipients |
title_short | Population pharmacokinetics of letermovir following oral and intravenous administration in healthy participants and allogeneic hematopoietic cell transplantation recipients |
title_sort | population pharmacokinetics of letermovir following oral and intravenous administration in healthy participants and allogeneic hematopoietic cell transplantation recipients |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965833/ https://www.ncbi.nlm.nih.gov/pubmed/33440077 http://dx.doi.org/10.1002/psp4.12593 |
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