Parkinson's Disease (PD) is a progressive neurologic disease caused by loss of dopaminergic neurons in the midbrain substantia nigra. Decreased activation of dopamine dependent motor pathways results in the classic features of PD including tremor, bradykinesia, rigidity, and gait impairment. The gold standard treatment of Parkinson's Disease (PD) is levodopa, which acts to replenish deficient endogenous dopamine production, combined with carbidopa, a decarboxylase inhibitor to decrease peripheral breakdown of levodopa.
Early in the disease, the combination of carbidopa and levodopa (CD-LD) works remarkably well, with stable symptom control lasting longer than four hours. However, as the disease progresses, the response to levodopa begins to shorten and mirrors the half-life of CD-LD (roughly 90 minutes). This leads to extended “off” time without symptom control, and shorter periods of “on” time.1 Increasing frequency and/or doses of levodopa may be used to prolong “on” time, but this leads to increased dopaminergic side effects including dyskinesia. Dyskinesia and other motor complications including wearing-off occur in up to 90% of patients treated with levodopa for 5-10 years.1 Patients may ultimately experience rapid cycling between states of dyskinesia and “off” time, with minimal “on” time.2
Strategies to combat this rapid cycling center on extending the half-life and bioavailability of levodopa or using adjunctive medications to prolong dopaminergic activity, increasing trough levels while reducing peak blood levels that lead to dyskinesia.2 The original controlled release carbidopa-levodopa tablets (CR, ER, SA) lack the ability to provide immediate symptom that is often needed.3 Entacapone co-administration may prolong “on” time in advanced PD patients,4 but has been associated with an increased incidence of dyskinesia in early PD patients in the STRIDE-PD trial.5
Liang, MD, Tsao-Wei; Weissfeld, MD, Ted A.; and Bober, Timothy
"New Developments in the Treatment of Parkinson's Disease: Bridging the gap between Medical and Surgical Therapy for PD,"
2, Article 4.
Available at: http://jdc.jefferson.edu/jhnj/vol11/iss2/4