Pressor response to oral tyramine during co-administration with safinamide in healthy volunteers

Abstract

The aim of this study was to evaluate the pressor response to oral tyramine during repeated administration of oral safinamide in healthy volunteers. Twelve females and eight males aged 52.7 ± 4.9years entered the study. An oral tyramine screening test was conducted to select subjects sensitive to the tyramine pressor effect on systolic blood pressure (SBP) in the dose range of 200-400mg. Safinamide 300mg was then administered once daily under fasting conditions. Starting on day5 (safinamide pharmacokinetic steady state), single ascending doses of tyramine were co-administered daily: 50, 100 and 200mg were administered on days5, 6 and 7, respectively. Vital parameters were monitored by telemetry. No SBP increase ≥30mmHg over baseline was observed when tyramine was co-administered with safinamide. Less than one third of the 400mg responders reported SBP increases between 22 and 27mmHg, which were below the threshold of 30mmHg over baseline. SBP increases, as well as time interval to pressor response measured after co-treatment with safinamide and tyramine 200mg, were not significantly different from those measured after administration of oral tyramine 200mg alone. Safinamide 300mg, administered o.d. under fasting conditions, does not change the tyramine pressor response as evaluated at steady state after 6-7days of treatment as compared with the effect of tyramine administered alone. Safinamide, which inhibits monoamine oxidase (MAO)-B, does not affect oral tyramine metabolism mediated mostly by the intestinal MAO-A.