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. 2023 Jun 8;15(6):1680.
doi: 10.3390/pharmaceutics15061680.

Pharmacokinetics of Venetoclax Co-Administered with Posaconazole in Patients with Acute Myeloid Leukemia

Simona De Gregori  1 , Eleonora Gelli  2 , Mara Capone  1 , Giulia Gambini  3 , Elisa Roncoroni  4 , Marianna Rossi  4 , Claudia Patricia Tobar Cabrera  2 , Gianluca Martini  2 , Ludovica Calabretta  2 , Luca Arcaini  2   4 , Riccardo Albertini  1 , Patrizia Zappasodi  4
Affiliations

Pharmacokinetics of Venetoclax Co-Administered with Posaconazole in Patients with Acute Myeloid Leukemia

Simona De Gregori et al. Pharmaceutics. .

Abstract

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.

Keywords: HPLC-MS/MS; acute myeloid leukemia; dose adjustment; elderly patients; pharmacokinetics; posaconazole; venetoclax.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
VEN and VEN-d7 chromatogram.
Figure 2
Figure 2
mean venetoclax (± SD) trough concentration (Cτ) during the first 12 days of treatment.
Figure 3
Figure 3
mean (±SD) venetoclax concentration profiles on day 7 and day 12.
Figure 4
Figure 4
Individual venetoclax AUC0-8 values on day 7 and day 12.
See this image and copyright information in PMC

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