PRESSER EFFECT OF ORAL TYRAMINE DURING TREATMENT WITH BEFLOXATONE, A NEW REVERSIBLE MONOAMINE OXIDASE-A INHIBITOR, IN HEALTHY-SUBJECTS

The interaction between tyramine and befloxatone, a new selective, rev ersible monoamine oxidase-A (MAO-A) inhibitor, was studied in a single -blind, parallel-group study in 30 healthy male volunteers whose fasti ng tyramine 30 dose (Tyr(30)) was 400 or 600 mg. Each subject complete d a placebo run-in period followed by a befloxatone period. Befloxaton e was given in repeated doses according to one of three regimens: befl oxatone 20 mg once daily at the end of a meal rich in tyramine or befl oxatone 10 or 20 mg twice daily 2 hours before a meal rich in tyramine . Subjects were given increasing daily doses of tyramine mixed with th e meal, until a systolic blood pressure increase of at least 30 mm Hg was achieved (Tyr(30)). The mean Tyr(30) decreased from 1220 mg (range , 600-1800 mg) during placebo to 290 mg (range, 150-500 mg) during bef loxatone 20 mg once daily, 250 mg (range, 100-300) during befloxatone 10 mg twice daily, and 155 mg (range, 100-250 mg) during befloxatone 2 0 mg twice daily; corresponding to a potentiation factor of 5.2-, 6.5- , and 7.9-fold, respectively. The extent and the duration of the systo lic blood pressure increase did not significantly differ between the p lacebo and the befloxatone regimens, except for a longer duration with the 20-mg twice daily regimen. These results are similar to those rep orted with the therapeutic dosage of other selective MAO-A inhibitors. They suggest that there would be little risk of hypertensive crisis i n patients treated in clinical studies with befloxatone, and thus diet ary restrictions appear to be unnecessary when the drug is given in a regimen of up to 20-mg once daily after meals.