The Effect of Safinamide, a Novel Drug for Parkinson's Disease, on Pressor Response to Oral Tyramine: A Randomized, Double‐Blind, Clinical Trial

This randomized, double‐blind, placebo‐, comparator (selegiline 10 mg/day)‐, and positive (phenelzine 30 mg/day)‐controlled study investigated the pressor response to oral tyramine under fasting conditions after the administration of safinamide at therapeutic (100 mg/day) and supratherapeutic (350 mg/day) dosing regimens in healthy volunteers for the purpose of assessing the need for dietary restrictions. Pressor response was characterized by Tyr30, defined as the tyramine dose that triggers a sustained increase in systolic blood pressure (SBP) of ≥30 mm Hg as compared with baseline SBP. The primary end point was the tyramine sensitivity factor (TSF), defined as the ratio of Tyr30 at screening to Tyr30 under treatment. Safinamide induced a mild increase in TSF; however, the effect at each of the doses was numerically lower than those of the comparators (geometric mean TSFs: placebo, 1.52; safinamide 100 mg, 2.15; safinamide 350 mg, 2.74; selegiline, 3.12; phenelzine, 9.98). This study confirms that safinamide is a highly selective monoamine oxidase‐B inhibitor, even at supratherapeutic doses, and suggests that it can be administered without tyramine‐related dietary restrictions. Clinical Pharmacology & Therapeutics (2012); 92 4, 450–457. doi: 10.1038/clpt.2012.128