Tolerability, safety, pharmacodynamics, and pharmacokinetics of rasagiline:: A potent, selective, and irreversible monoamine oxidase type B inhibitor

Study Objective. To investigate the tolerability, safety, pharmacodynamics, and pharmacokinetics of rasagiline after once-daily oral administration of single or repeated doses. Design. A randomized, double-blind, placebo-controlled, three-way, singledose study and a randomized, double-blind, placebo-controlled, repeated-dose study. Setting. Clinical research center in France. Subjects. Healthy male volunteers aged 18-40 years (12 in the single-dose study, 24 in the repeated-dose study). Intervention. In the single-dose study, subjects received, in a randomized sequence, single doses of placebo, rasagiline 1 mg, and rasagiline 5 mg; or placebo, rasagiline 2 mg, and rasagiline 10 mg. Six subjects received an additional single dose of rasagiline 20 mg. There was a 2-week washout period between each dose. In the repeated-dose study, subjects were randomized to receive rasagiline 2 mg, 5 mg, or 10 mg, or placebo once/day for 10 days. Measurements and Main Results. To assess tolerability and safety, patients underwent physical examinations, vital sign measurements, 12-lead electrocardiograms, clinical laboratory testing, and bleeding time studies. To determine platelet monoamine oxidase type B (MAO-B) activity and rasagiline pharmacokinetics, blood and urine samples were taken. In the single-dose study, rasagiline 1-20 mg was well tolerated. Each dose significantly inhibited platelet MAO-B activity. In the repeated-dose study, all doses of rasagiline were well tolerated; almost full inhibition of platelet MAO-B activity was achieved with each rasagiline dose. Conclusion. Rasagiline is well tolerated at doses up to 20 mg once/day and is a potent inhibitor of platelet MAO-B in humans.