1. Paired comparisons of venetoclax concentration in cerebrospinal fluid, bone marrow, and plasma in acute leukemia patients.
- Author
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Jian Y, Han F, Zhu Y, Geng C, Zhang Y, Wu Y, Leng Y, Chen W, An Z, and Zhu HH
- Subjects
- Humans, Male, Middle Aged, Female, Aged, Adult, Antineoplastic Agents administration & dosage, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents cerebrospinal fluid, Antineoplastic Agents blood, Tandem Mass Spectrometry, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute cerebrospinal fluid, Leukemia, Myeloid, Acute blood, Aged, 80 and over, Chromatography, Liquid, Leukemia drug therapy, Leukemia cerebrospinal fluid, Leukemia blood, Young Adult, Bridged Bicyclo Compounds, Heterocyclic pharmacokinetics, Bridged Bicyclo Compounds, Heterocyclic administration & dosage, Bridged Bicyclo Compounds, Heterocyclic cerebrospinal fluid, Bridged Bicyclo Compounds, Heterocyclic blood, Sulfonamides administration & dosage, Sulfonamides pharmacokinetics, Sulfonamides cerebrospinal fluid, Sulfonamides blood, Bone Marrow drug effects
- Abstract
Venetoclax, a small molecule inhibitor of BCL-2, has demonstrated efficacy in treating acute leukemias and has been recommended as one of the first-line anti-leukemia therapies. Although venetoclax has been suggested to probably possess the ability to penetrate the central nervous system (CNS), current data to elucidate the characteristics of venetoclax in cerebrospinal fluid (CSF), bone marrow (BM), and plasma are still lacking. This study investigated the real-world characteristics of venetoclax concentrations in CSF, BM, and plasma in acute leukemia patients. Thirteen acute leukemia patients treated with venetoclax were included, with paired samples of CSF, BM, and plasma collected and venetoclax concentrations measured using LC-MS/MS. With the results, the median venetoclax concentrations were 2030 ng/mL in plasma, 16.7 ng/mL in CSF, and 1390 ng/mL in BM. The percentages of CSF/plasma and BM/plasma were 0.74% and 70.37%, respectively. While no direct correlation was observed between CSF and plasma venetoclax levels, there was a trend toward an improved CSF/plasma percentage over time following the last administration of venetoclax. In contrast, a strong correlation was found between BM and plasma levels. This study demonstrated that venetoclax could reach its effective concentration in most patients, suggesting its potential clinical utility in the management of CNS involvement in acute leukemia., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
- Published
- 2024
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