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January 1989

Plasma Physostigmine Concentrations After Controlled-Release Oral Administration

Arch Neurol. 1989;46(1):13. doi:10.1001/archneur.1989.00520370015007

To the Editor.  —The development of an effective agent to increase brain levels of acetylcholine in patients with the memory disorder of Alzheimer's disease, who are known to be deficient in brain acetylcholine, is of utmost importance. Clinical trials with immediate-release physostigmine salicylate, which inhibits enzymatic degradation of acetylcholine, have been reported to be beneficial,1,2 equivocal,3 or negative4 in Alzheimer's disease. Immediate-release physostigmine salicylate has an extremely short plasma half-life of approximately 30 minutes,5,6 which limits bioavailability of physostigmine for uptake into the brain. Many of the reMean plasma physostigmine concentrations in five young healthy male volunteers after oral physostigmine salicylate administration: closed circles indicate 2-mg immediate-release physostigmine salicylate; open circles, 9-mg controlled-release (CR) physostigmine salicylate; open rectangle, 12-mg CR physostigmine salicylate; and open triangle, 15-mg CR physostigmine salicylate. ported studies failed to monitor the bioavailability of this compound. The development of a controlled-release formulation