Influence of food on the disposition of the monoamine oxidase-A inhibitor brofaromine in healthy volunteers.
The effect of food on the bioavailability of brofaromine hydrochloride was investigated in a randomized cross-over study. Eight healthy male volunteers were given single peroral doses of 75 mg brofaromine hydrochloride after overnight fasting or a fat- and protein-rich breakfast. Mean (+/- SD) areas under the plasma concentration-time curves (AUC) were 9.66 (2.35) mumol l-1 h when given to the fasted volunteers and 11.82 (3.78) mumol l-1 h (p = 0.0413) when given after a substantial breakfast. Mean (+/- SD) maximum plasma concentrations (Cmax) were 0.71 (0.13) mumol l-1 when given to the fasted volunteers and 0.85 (0.22) mumol l-1 (p > 0.05) when given after breakfast. Thus, both the average AUC and Cmax were increased by approximately 20 per cent when brofaromine hydrochloride was given with food. The times when Cmax was reached (tmax) as well as the elimination half-lives were not influenced by concomitant intake of food. The tolerability was the same whether brofaromine was given before or after food in healthy volunteers. The slight effect of food on the bioavailability of brofaromine should be of little therapeutic consequence because of the observed wide inter-subject variability of the plasma levels.
Degen
P H
PH
CIBA-GEIGY Limited, Pharma Research and Development Department, Basle, Switzerland.
Cardot
J M
JM
Czendlik
C
C
Dieterle
W
W
D000328:Adult; D001682:Biological Availability; D002849:Chromatography, Gas; D005502:Food; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics*; D010880:Piperidines / Q000009:adverse effects / Q000493:pharmacokinetics*
D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; C038213:brofaromine; D008995:Monoamine Oxidase