Is 10 milligrams selegiline essential as an adjunct therapy for the symptomatic treatment of Parkinson's disease?
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.
Mahmood
I
I
Office of Clinical Pharmacology and Biopharmaceutics, Division of Pharmaceutical Evaluation I, Food and Drug Administration, Rockville, Maryland 20852, USA.
D001792:Blood Platelets / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010300:Parkinson Disease / Q000188:drug therapy*; D012642:Selegiline / Q000008:administration & dosage* / Q000493:pharmacokinetics
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D007980:Levodopa; D008995:Monoamine Oxidase