INHIBITION OF ACETYLCHOLINESTERASE BY DISTIGMINE BROMIDE (UBRETID)

A randomized phase-I study was performed in a clinical setting in 24 h ealthy young male subjects, aged 20 to 35 years, to investigate the in fluence of Ubretid on AChE inhibition following oral and i. m. adminis tration in one of three medication schemes: - single oral (10 mg) and i. m. (0.5 mg) medication (randomized crossover), - multiple oral dosi ng (5 mg on trial days 1, 2, 3, 5, 7, 9, 11 and 13), - multiple oral d osing (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 wer e chosen as they are both frequently used in clinical practice. The re sults of the AChE inhibition after Ubretid can be summarized as follow s: 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 indicatio n of an increased AChE inhibition towards the end of treatment. Compar ed with the i.m. administration, the Ubretid tablet had a bioavailabil ity of 2.2 +/- 1.1%.(mean +/- STD).