EEG, MAO-A INHIBITION, PHARMACOKINETICS AND SAFETY OF BEFLOXATONE IN THE ELDERLY

Befloxatone is a new reversible and selective MAO-A inhibitor. The pre sent study aimed to assess the pharmacodynamics (EEG profile and MAO-A inhibition using plasma levels of DHPG), pharmacokinetics and safety after a single dose of 10 mg of befloxatone compared to amitriptyline 50 mg in a randomized, double-blind, three-way crossover, placebo-cont rolled trial involving 12 elderly subjects. Befloxatone did not show a ny sedative profile on EEG as no significant changes occurred in slow delta and theta waves or in alpha waves. In contrast, befloxatone prod uced a non-significant decrease in delta relative power and a signific ant increase in the (12-40 Hz) beta waves compared to placebo and/or a mitriptyline depending on the EEG lead. MAO-A inhibition by befloxaton e was evidenced by a significant reduction in DHPG plasma levels (peak activity of -85 per cent and AUC(0-24 h) of -46 per cent compared to placebo). The pharmacokinetics parameters obtained after a single 10-m g oral dose of befloxatone were: t(max), 2 h; C-max, 33.7 ng/ml; t(1/2 )beta, 14.5 h; AUC(0-infinity), 255 ng/ml for befloxatone and t(max), 2 h; C-max, 29.4 ng/ml; t(1/2)beta, 16 h; AUC(0-infinity), 596 ng/ml f or its main metabolite, O-demethyl befloxatone. These parameters are i n the same range as those obtained in healthy young subjects. In concl usion, the present study demonstrated that a single oral dose of 10 mg of befloxatone is safe in the elderly, possesses potent MAO-A inhibit ion activity and the EEG profile of a non-sedative antidepressant and did not justify dose adjustment compared to young subjects. (C) 1997 J ohn Wiley & Sons, Ltd.