L-Deprenyl, levodopa pharmacokinetics, and response fluctuations in Parkinson's disease

Six patients with Parkinson's disease (PD) and therapeutic response fluctuations (RF) on levodopa treatment participated in an open-label trial of L-deprenyl (Eldepryl) in conjunction with Sinemet. Deprenyl (10 mg/day) allowed a slight but not statistically significant 22% reduction of total daily levodopa intake after 4 weeks of treatment, with a significant but unsustained reduction in the number of daily 'off' periods and an increase in the portion of waking day spent 'on'. Pharmacokinetic studies revealed no effect of deprenyl on the plasma levodopa concentration vs. time curve, or the coefficient of variation (C.V.) of plasma levodopa levels measured over an 8-h period. Plasma DOPAC levels were unaffected, suggesting that the majority of peripheral DOPAC is generated by action of MAO-A. For most patients, benefit was not maintained. Two patients have continued taking the drug, and both have enjoyed significant reductions in total levodopa dose. Both have mild end-of-dose failure and little dyskinesia. Since no changes in peripheral pharmacokinetics of levodopa could be demonstrated, any therapeutic action of deprenyl in PD would appear to be due to prolongation of dopaminergic activity within the CNS.