ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2023; 14(7):1151-1156. doi:10.7150/jca.81795 This issue Cite
Research Paper
Venetoclax Penetrates the Blood Brain Barrier: A Pharmacokinetic Analysis in Pediatric Leukemia Patients
1. AbbVie, Inc, North Chicago, IL, USA.
2. Dana-Farber/Boston Children's Cancer & Blood Disorders Center, Boston, MA, USA.
3. Genentech, Inc, South San Francisco, CA, USA.
4. Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
5. Cancer and Blood Disorders Center, Seattle Children's Hospital, Seattle, Washington, USA.
6. Clinical Pharmacy, Ain Shams University, Cairo, Egypt.
* Affiliation of author at the time this work was conducted
Abstract
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.
Keywords: venetoclax, pharmacokinetics, blood-brain barrier, cerebrospinal fluid, central nervous system.
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