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Tolerability, Safety, Pharmacodynamics, and Pharmacokinetics of Rasagiline: A Potent, Selective, and Irreversible Monoamine Oxidase Type B Inhibitor

2004; Wiley; Volume: 24; Issue: 10 Linguagem: Inglês

10.1592/phco.24.14.1295.43156

1875-9114

John J. Thébault, Michel Guillaume, R. Levy,

Parkinson's Disease Mechanisms and Treatments

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, single‐dose 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.