Intrathecally administered m-AMSA in the rhesus monkey.
4'-(9-Acridinylamino)-methanesulfon-m-anisidide (m-AMSA) is an acridine compound that has been found useful in the systemic treatment of acute leukemia. This paper specifically investigates the CSF pharmacokinetics of m-AMSA following both intravenous and intraventricular administration in a subhuman primate model. Following intravenous administration, m-AMSA crossed the blood-brain barrier poorly; cerebrospinal fluid (CSF) concentrations were only 1-3% of systemic concentrations. Intraventricular administration of drug achieved high initial ventricular fluid concentrations, but the drug was rapidly cleared with a half-life of 115 min. Following 500 micrograms of intraventricular drug, CSF concentrations of m-AMSA remained above 1 microM for only 6 h. These data suggest that m-AMSA has potential as an intrathecal agent against meningeal leukemia refractory to more conventional therapy, but detailed toxicology and neurohistopathology will be required before intra-CSF m-AMSA can be considered for human use.
D000609:Aminoacridines / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid; D000677:Amsacrine; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008253:Macaca mulatta; D008297:Male
D000609:Aminoacridines; D000970:Antineoplastic Agents; D000677:Amsacrine