Effects of a tyramine-enriched meal on blood pressure response in healthy male volunteers treated with selegiline transdermal system 6 mg/24 hour.
BACKGROUND
Monoamine oxidase inhibitors are well recognized as effective antidepressant agents but are rarely used due, in part, to the risk of hypertensive crisis following the ingestion of foods high in tyramine ("cheese reaction"). A selegiline transdermal system (STS) was developed to provide antidepressant concentrations of selegiline in the brain, while preserving the gastrointestinal monoamine oxidase A (MAO-A) barrier. The present study was conducted to determine the effect of the STS 6 mg/24 hour on cardiovascular safety following the ingestion of approximately 400 mg of tyramine consumed as a component of aged cheeses.


METHODS
In this open-label, single-center phase I study, cardiovascular vital signs were recorded following tyramine challenges during placebo and STS 6 mg/24 hr treatment. Subjects were observed for clinical signs and symptoms of a pressor response and/or potential hypertensive crisis during and following the challenges.


RESULTS
Ingestion of tyramine-enriched meals following 13 consecutive days of treatment with the STS 6 mg/24 hr (pharmacokinetic steady-state) produced no clinically significant changes in cardiovascular vital signs in 12 healthy adult male subjects. No evidence of a tyramine pressor effect on systolic blood pressure or evidence of hypertensive crisis occurred during the STS treatment.


CONCLUSIONS
These results suggest that STS 6 mg/24 hr may be administered without concern for dietary tyramine consumption.
Blob
Lawrence F
LF
Somerset Pharmaceuticals, Tampa, FL 33607, USA.
Sharoky
Melvin
M
Campbell
Bryan J
BJ
Kemper
Eva M
EM
Gilmor
Michelle Gilmor
MG
VanDenberg
Chad M
CM
Azzaro
Albert J
AJ
D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D002611:Cheese; D004311:Double-Blind Method; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D012642:Selegiline / Q000008:administration & dosage / Q000494:pharmacology*; D014439:Tyramine / Q000494:pharmacology*
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D014439:Tyramine