Venetoclax Penetrates the Blood Brain Barrier: A Pharmacokinetic Analysis in Pediatric Leukemia Patients.

Autor:	Badawi M; AbbVie, Inc, North Chicago, IL, USA., Menon R; AbbVie, Inc, North Chicago, IL, USA., Place AE; Dana-Farber/Boston Children's Cancer & Blood Disorders Center, Boston, MA, USA., Palenski T; AbbVie, Inc, North Chicago, IL, USA., Sunkersett G; AbbVie, Inc, North Chicago, IL, USA., Arrendale R; AbbVie, Inc, North Chicago, IL, USA., Deng R; Genentech, Inc, South San Francisco, CA, USA., Federico SM; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA., Cooper TM; Cancer and Blood Disorders Center, Seattle Children's Hospital, Seattle, Washington, USA., Salem AH; AbbVie, Inc, North Chicago, IL, USA.; Clinical Pharmacy, Ain Shams University, Cairo, Egypt.
Jazyk:	angličtina
Zdroj:	Journal of Cancer [J Cancer] 2023 Apr 25; Vol. 14 (7), pp. 1151-1156. Date of Electronic Publication: 2023 Apr 25 (Print Publication: 2023).
DOI:	10.7150/jca.81795
Abstrakt:	Infiltration of malignant cells into the central nervous system in hematological malignancies correlates with poor clinical outcomes. Investigations into the penetration of venetoclax into the central nervous system have been limited. We report venetoclax pharmacokinetics in plasma and cerebrospinal fluid samples from a Phase 1 study in pediatric patients with relapsed or refractory malignancies that demonstrate venetoclax ability to cross into the central nervous system. Venetoclax was detected in cerebrospinal fluid (CSF) samples, with concentrations ranging from < 0.1 to 26 ng/mL (mean, 3.6 ng/mL) and a plasma:CSF ratio ranging from 44 to 1559 (mean, 385). Plasma:CSF ratios were comparable among patients with AML and ALL and no clear trend was observed in the ratios over the course of treatment. Moreover, improvement in central nervous system (CNS) involvement status was observed in patients who had measurable concentrations of venetoclax in the CSF. CNS resolution was observed for up to six months while on treatment. These findings highlight the potential role of venetoclax and provide the opportunity to further investigate its utility in improving clinical outcomes for patients with CNS complications. Competing Interests: Competing Interests: MB, RM, RA, and AHS are employees of AbbVie Inc. and may hold AbbVie stock and/or stock options. TP is a former employee of AbbVie and may hold AbbVie stock and/or stock options. RD is an employee of Genentech Inc. and may hold Roche stock or stock options. TC declares no competing interests. (© The author(s).)
Databáze:	MEDLINE
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