Abstract
Selegiline is used as an adjunct to levodopa in the symptomatic treatment of Parkinson's disease (PD). The normal daily dose of selegiline is 10 mg administered orally. This study, based on monoamine oxidase-B (MAO-B) inhibition, investigates whether a reduction in selegiline dose can provide the same beneficial effects seen with a 10-mg dose. The inhibition of platelet MAO-B activity against multiple dosing of selegiline (2.5, 5, and 7.5 mg) was predicted from the data obtained from literature (0.5, 1.0, 1.5, and 10 mg). A pharmacokinetic-pharmacodynamic model for selegiline was also developed. The data suggested that by 96 hours (four doses) the inhibition of platelet MAO-B activity is approximately 95% after a daily dose of 2.5 mg selegiline, whereas it takes only 48 hours (two doses) for doses of 5 mg and 7.5 mg to achieve this degree of inhibition. The pharmacokinetic-pharmacodynamic model was best described by a sigmoidal Emax 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 therapeutic effect. Therefore, lower doses of selegiline should be tested in clinical trials.
Published Version
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