To improve the management of spiromustine neurotoxicity in cancer patients who presently have to receive physostigmine injections hourly for up to 72 hours after a dose of spiromustine, a study was designed to exploit the possibility of replacing the parenteral physostigmine with an oral dosage form. The oral physostigmine study will be part of ongoing Phase I and II investigations of spiromustine for the treatment of CNS tumors. A published high-performance liquid chromatographic method for the determination of physostigmine in plasma is presently being evaluated for possible application in our study. If oral physostigmine proves to be equally effective clinically in controlling spiromustine neurotoxicity, tablets will replace the parenteral injections in patient management. Characterization of oral physostigmine bioavailability and plasma elimination kinetics in patients will precede any clinical decision on dosage from change.
