The DuPont Merck Pharmaceutical Company has received approval to market Sinemet CR (carbidopa-levodopa, sustained-release), the first sustainedrelease treatment for the signs and symptoms of Parkinson's disease available in the United States.
The original formulation, Sinemet (carbidopa-levodopa), has been the foundation of therapy since the mid-1970s. With the new sustained-release delivery, many patients may receive more continuous benefit, yet take the medication less frequently.
Parkinson's disease patients often experience unpredictable fluctuations between mobility and immobility, known as "on-off" effects. These clinical fluctuations can occur rapidly and present serious obstacles to patients with advanced parkinsonism. Sinemet CR provides patients with more steady blood levodopa levels than does the standard Sinemet therapy.
Patients treated with levodopa therapy for Parkinson's disease may develop motor fluctuations characterized by endof-dose failure, peak dose dyskinesia, and akinesia. The advanced form of motor fluctuations is characterized by unpredictable swings from mobility to immobility. It should be noted that in clinical trials, patients with moderate to severe motor fluctuations who received Sinemet CR did not experience quantitatively significant reductions in "off time" when compared with Sinemet (carbidopa-levodopa). Although the cause of the motor fluctuations is not completely understood, in some patients they may be attenuated by treatment regimens that produce steady plasma levels of levodopa.
In addition, in clinical trials, global ratings of improvement as assessed by both patients and physicians were better during therapy with Sinemet CR than with Sinemet. In patients without motor fluctuations, Sinemet CR, under controlled conditions, provided the same therapeutic benefit with less frequent dosing when compared with Sinemet.
The exact cause of Parkinson's disease is unknown, but researchers do know that patients exhibit a shortage of the chemical dopamine, a substance that transmits messages to the part of the brain regulating movement. Dopamine deficiency may result in a resting tremor, rigidity, and temporary immobility.
Levodopa, the precursor to dopamine, is considered the most effective therapy currently available for control of Parkinson's disease symptoms. Sinemet CR contains levodopa and carbidopa. Carbidopa permits more levodopa to cross the blood-brain barrier while reducing certain side effects, such as nausea, experienced when levodopa is used alone.
The sustained-release formulation provides many patients with better global improvements. Sinemet CR produces lower peak levels of levodopa by smoothing out the peaks and troughs in blood levels of levodopa; the sustainedrelease formulation provides many patients with improved global function.
For more information, contact Roger Morris, Du Pont Pharmaceuticals, PO Box 80026, Wilmington, DE 198800026; 302-992-4747.