EEG, MAO-A inhibition, pharmacokinetics and safety of befloxatone in the elderly

Befloxatone is a new reversible and selective MAO-A inhibitor. The present 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-controlled trial involving 12 elderly subjects. Befloxatone did not show any sedative profile on EEG as no significant changes occurred in slow delta and theta waves or in alpha waves. In contrast, befloxatone produced a non-significant decrease in delta relative power and a significant increase in the (12-40 Hz) beta waves compared to placebo and/or amitriptyline depending on the EEG lead. MAO-A inhibition by befloxatone 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-mg 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 for its main metabolite, O-demethyl befloxatone. These parameters are in the same range as those obtained in healthy young subjects. In conclusion, the present study demonstrated that a single oral dose of 10 mg of befloxatone is safe in the elderly, possesses potent MAO-A inhibition activity and the EEG profile of a non-sedative antidepressant and did not justify dose adjustment compared to young subjects. (C) 1997 John Wiley & Sons, Ltd.