Intrathecally administered m-AMSA in the rhesus monkey

Area of Science:

• Pharmacology
• Neuroscience
• Oncology

Background:

• 4'-(9-Acridinylamino)-methanesulfon-m-anisidide (m-AMSA) is an acridine compound utilized in acute leukemia treatment.
• Investigating drug delivery to the central nervous system is crucial for treating neurological complications of cancer.

Purpose of the Study:

• To determine the cerebrospinal fluid (CSF) pharmacokinetics of m-AMSA.
• To evaluate m-AMSA's potential as an intrathecal agent for meningeal leukemia.

Main Methods:

• Subhuman primate model used for pharmacokinetic studies.
• Intravenous and intraventricular administration routes assessed.
• CSF and plasma concentrations of m-AMSA were measured over time.

Main Results:

• Intravenous m-AMSA demonstrated poor penetration across the blood-brain barrier (1-3% of systemic concentrations in CSF).
• Intraventricular administration resulted in high initial concentrations but rapid clearance (115 min half-life).
• CSF concentrations remained above 1 microM for only 6 hours after intraventricular administration of 500 micrograms.

Conclusions:

• m-AMSA shows potential as an intrathecal agent for meningeal leukemia resistant to conventional therapies.
• Further toxicological and neurohistopathological studies are necessary before human intra-CSF m-AMSA administration.