IS 10 MILLIGRAMS SELEGILINE ESSENTIAL AS AN ADJUNCT THERAPY FOR THE SYMPTOMATIC TREATMENT OF PARKINSONS-DISEASE

Selegiline is used as an adjunct to levodopa in the symptomatic treatm ent of Parkinson's disease (PD). The normal daily dose of selegiline i s 10 mg administered orally. This study, based on monoamine oxidase-B (MAO-B) inhibition, investigates whether a reduction in selegiline dos e can provide the same beneficial effects seen with a 10-mg dose. The inhibition of platelet MAO-B activity against multiple dosing of seleg iline (2.5, 5, and 7.5 mg) was predicted from the data obtained from l iterature (0.5, 1.0, 1.5, and 10 mg). A pharmacokinetic-pharmacodynami c model for selegiline was also developed. The data suggested that by 96 hours (four doses) the inhibition of platelet MAO-B activity is app roximately 95% after a daily dose of 2.5 mg selegiline, whereas it tak es only 48 hours (two doses) for doses of 5 mg and 7.5 mg to achieve t his degree of inhibition. The pharmacokinetic-pharmacodynamic model wa s best described by a sigmoidal E-max model with an effect compartment . Based on the inhibition of MAO-B activity, a reduction in daily oral dose of selegiline appears possible without compromising the therapeu tic effect. Therefore, lower doses of selegiline should be tested in c linical trials.