Pharmacokinetic and pharmacodynamic interaction between toloxatone, a new reversible monoamine oxidase-A inhibitor, and oral tyramine in healthy subjects.
We examined the influence of toloxatone, a new reversible monoamine oxidase-A inhibitor used in the treatment of depression, on tyramine-induced pressor effect in healthy volunteers. The maximum increase in systolic blood pressure produced by four single oral doses of tyramine administered during a meal and ranging from 100 mg to 800 mg was compared during repeated (3 to 5 days) administration of placebo, 200 mg toloxatone three times a day and 400 mg toloxatone three times a day in a single-blind, three-period crossover study. Toloxatone by itself had no significant influence on blood pressure. During administration of toloxatone, no significant increase in tyramine-induced increase in systolic blood pressure was observed for tyramine doses of 200 mg or less that are consistently higher than those associated with normal food intake. However, toloxatone increased the tyramine-induced increase in blood pressure after 400 mg tyramine (400 mg toloxatone three times a day) and 800 mg tyramine (200 mg toloxatone three times a day and 400 mg toloxatone three times a day). This pharmacodynamic interaction could be explained by an increase in tyramine systemic bioavailability in the presence of toloxatone. It is concluded that interaction between tyramine in meals and toloxatone is unlikely to occur in patients after long-term administration of the drug at therapeutic dosages.
Provost
J C
JC
Clinical Pharmacology Unit, Saint-Antoine University Hospital, Paris, France.
Funck-Brentano
C
C
Rovei
V
V
D'Estanque
J
J
Ego
D
D
Jaillon
P
P
D000284:Administration, Oral; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects*; D004357:Drug Synergism; D006801:Humans; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D010080:Oxazoles / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D023303:Oxazolidinones; D012016:Reference Values; D016037:Single-Blind Method; D014439:Tyramine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*
D008996:Monoamine Oxidase Inhibitors; D010080:Oxazoles; D023303:Oxazolidinones; C010798:toloxatone; D014439:Tyramine