Inhibition of acetylcholinesterase by distigmine bromide (Ubretid)

A randomized phase-I study was performed in a clinical setting in 24 healthy young male subjects, aged 20 to 35 years, to investigate the influence of Ubretid on AChE inhibition following oral and i.m. administration in one of three medication schemes: -single oral (10 mg) and i.m. (0.5 mg) medication (randomized crossover), -multiple oral dosing (5 mg on trial days 1, 2, 3, 5, 7, 9, 11 and 13), -multiple oral dosing (5 mg on trial days 5 to 14) with initial i.m. loading doses (0.5 mg i.m. on trial days 1, 2 and 4). The multiple dosing schemes were chosen as they are both frequently used in clinical practice. The results of the AChE inhibition after Ubretid can be summarized as follows: repeated Ubretid administration as used in this trial did not lead to a cumulation of AChE inhibition. Statistical testing (page test) of maximum AChE inhibition on the last medication days gave no indication of an increased AChE inhibition towards the end of treatment. Compared with the i.m. administration, the Ubretid tablet had a bioavailability of 2.2 +/- 1.1% (mean +/- STD).