Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785065212912599040
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
work_keys_str_mv AT degregorisimona pharmacokineticsofvenetoclaxcoadministeredwithposaconazoleinpatientswithacutemyeloidleukemia
AT gellieleonora pharmacokineticsofvenetoclaxcoadministeredwithposaconazoleinpatientswithacutemyeloidleukemia
AT caponemara pharmacokineticsofvenetoclaxcoadministeredwithposaconazoleinpatientswithacutemyeloidleukemia
AT gambinigiulia pharmacokineticsofvenetoclaxcoadministeredwithposaconazoleinpatientswithacutemyeloidleukemia
AT roncoronielisa pharmacokineticsofvenetoclaxcoadministeredwithposaconazoleinpatientswithacutemyeloidleukemia
AT rossimarianna pharmacokineticsofvenetoclaxcoadministeredwithposaconazoleinpatientswithacutemyeloidleukemia
AT tobarcabreraclaudiapatricia pharmacokineticsofvenetoclaxcoadministeredwithposaconazoleinpatientswithacutemyeloidleukemia
AT martinigianluca pharmacokineticsofvenetoclaxcoadministeredwithposaconazoleinpatientswithacutemyeloidleukemia
AT calabrettaludovica pharmacokineticsofvenetoclaxcoadministeredwithposaconazoleinpatientswithacutemyeloidleukemia
AT arcainiluca pharmacokineticsofvenetoclaxcoadministeredwithposaconazoleinpatientswithacutemyeloidleukemia
AT albertiniriccardo pharmacokineticsofvenetoclaxcoadministeredwithposaconazoleinpatientswithacutemyeloidleukemia
AT zappasodipatrizia pharmacokineticsofvenetoclaxcoadministeredwithposaconazoleinpatientswithacutemyeloidleukemia