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Pharmacokinetics of Venetoclax Co-Administered with Posaconazole in Patients with Acute Myeloid Leukemia
The Food and Drug Administration currently approves the combination of hypomethylating agents (HMA), azacytidine or decitabine with venetoclax (VEN) for acute myeloid leukemia (AML) patients aged more than 75 years and for patients unsuitable for intensive chemotherapy. The risk of fungal infection...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303160/ https://www.ncbi.nlm.nih.gov/pubmed/37376128 http://dx.doi.org/10.3390/pharmaceutics15061680 |
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author | De Gregori, Simona Gelli, Eleonora Capone, Mara Gambini, Giulia Roncoroni, Elisa Rossi, Marianna Tobar Cabrera, Claudia Patricia Martini, Gianluca Calabretta, Ludovica Arcaini, Luca Albertini, Riccardo Zappasodi, Patrizia |
author_facet | De Gregori, Simona Gelli, Eleonora Capone, Mara Gambini, Giulia Roncoroni, Elisa Rossi, Marianna Tobar Cabrera, Claudia Patricia Martini, Gianluca Calabretta, Ludovica Arcaini, Luca Albertini, Riccardo Zappasodi, Patrizia |
author_sort | De Gregori, Simona |
collection | PubMed |
description | The Food and Drug Administration currently approves the combination of hypomethylating agents (HMA), azacytidine or decitabine with venetoclax (VEN) for acute myeloid leukemia (AML) patients aged more than 75 years and for patients unsuitable for intensive chemotherapy. The risk of fungal infection in the early phase of treatment is not negligible; therefore, posaconazole (PCZ) is commonly administered as primary prophylaxis. A drug–drug interaction between VEN and PCZ is well known, but the trend of serum levels of venetoclax when both drugs are overlapped is not clear. In total, 165 plasma samples from 11 elderly AML patients receiving combined treatment with HMA, VEN and PCZ were analyzed by a validated analytical method (high-pressure liquid chromatography–tandem mass spectrometry). Venetoclax trough plasma concentrations were detected during the 3 days of ramp-up as well as on day 7 and day 12 of treatment when the exposure as the area under the plasma concentration–time curve and the accumulation ratio were also calculated. The results were compared with the expected data for 400 mg/dose VEN administered alone—the confirmed high inter-individual variability in pharmacokinetics suggests the need for therapeutic drug monitoring. |
format | Online Article Text |
id | pubmed-10303160 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103031602023-06-29 Pharmacokinetics of Venetoclax Co-Administered with Posaconazole in Patients with Acute Myeloid Leukemia De Gregori, Simona Gelli, Eleonora Capone, Mara Gambini, Giulia Roncoroni, Elisa Rossi, Marianna Tobar Cabrera, Claudia Patricia Martini, Gianluca Calabretta, Ludovica Arcaini, Luca Albertini, Riccardo Zappasodi, Patrizia Pharmaceutics Article The Food and Drug Administration currently approves the combination of hypomethylating agents (HMA), azacytidine or decitabine with venetoclax (VEN) for acute myeloid leukemia (AML) patients aged more than 75 years and for patients unsuitable for intensive chemotherapy. The risk of fungal infection in the early phase of treatment is not negligible; therefore, posaconazole (PCZ) is commonly administered as primary prophylaxis. A drug–drug interaction between VEN and PCZ is well known, but the trend of serum levels of venetoclax when both drugs are overlapped is not clear. In total, 165 plasma samples from 11 elderly AML patients receiving combined treatment with HMA, VEN and PCZ were analyzed by a validated analytical method (high-pressure liquid chromatography–tandem mass spectrometry). Venetoclax trough plasma concentrations were detected during the 3 days of ramp-up as well as on day 7 and day 12 of treatment when the exposure as the area under the plasma concentration–time curve and the accumulation ratio were also calculated. The results were compared with the expected data for 400 mg/dose VEN administered alone—the confirmed high inter-individual variability in pharmacokinetics suggests the need for therapeutic drug monitoring. MDPI 2023-06-08 /pmc/articles/PMC10303160/ /pubmed/37376128 http://dx.doi.org/10.3390/pharmaceutics15061680 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article De Gregori, Simona Gelli, Eleonora Capone, Mara Gambini, Giulia Roncoroni, Elisa Rossi, Marianna Tobar Cabrera, Claudia Patricia Martini, Gianluca Calabretta, Ludovica Arcaini, Luca Albertini, Riccardo Zappasodi, Patrizia Pharmacokinetics of Venetoclax Co-Administered with Posaconazole in Patients with Acute Myeloid Leukemia |
title | Pharmacokinetics of Venetoclax Co-Administered with Posaconazole in Patients with Acute Myeloid Leukemia |
title_full | Pharmacokinetics of Venetoclax Co-Administered with Posaconazole in Patients with Acute Myeloid Leukemia |
title_fullStr | Pharmacokinetics of Venetoclax Co-Administered with Posaconazole in Patients with Acute Myeloid Leukemia |
title_full_unstemmed | Pharmacokinetics of Venetoclax Co-Administered with Posaconazole in Patients with Acute Myeloid Leukemia |
title_short | Pharmacokinetics of Venetoclax Co-Administered with Posaconazole in Patients with Acute Myeloid Leukemia |
title_sort | pharmacokinetics of venetoclax co-administered with posaconazole in patients with acute myeloid leukemia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303160/ https://www.ncbi.nlm.nih.gov/pubmed/37376128 http://dx.doi.org/10.3390/pharmaceutics15061680 |
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