Tolerability, safety, pharmacodynamics, and pharmacokinetics of rasagiline: a potent, selective, and irreversible monoamine oxidase type B inhibitor.
OBJECTIVE
To investigate the tolerability, safety, pharmacodynamics, and pharmacokinetics of rasagiline after once-daily oral administration of single or repeated doses.


METHODS
A randomized, double-blind, placebo-controlled, three-way, single-dose study and a randomized, double-blind, placebo-controlled, repeated-dose study.


METHODS
Clinical research center in France.


METHODS
Healthy male volunteers aged 18-40 years (12 in the single-dose study, 24 in the repeated-dose study).


METHODS
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.


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.


CONCLUSIONS
Rasagiline is well tolerated at doses up to 20 mg once/day and is a potent inhibitor of platelet MAO-B in humans.
Thébault
John J
JJ
GES, Brussels, Belgium
Guillaume
Michel
M
Levy
Ruth
R
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D001682:Biological Availability; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D002395:Catecholamines / Q000652:urine; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008657:Metabolic Clearance Rate; D008996:Monoamine Oxidase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology
D002395:Catecholamines; D007189:Indans; D008996:Monoamine Oxidase Inhibitors; C031967:rasagiline