Controlled‐release carbidopa/levodopa (CR4‐Sinemet) in Parkinson's disease patients with and without motor fluctuations

Abstract

Sixteen patients with advanced Parkinson's disease (PD) and motor fluctuations were evaluated throughout 12 months of open label therapy on CR4-Sinemet. Reduced dosage frequency and significant motor improvement with reduced fluctuation occurred and were maintained with CR4-Sinemet compared with baseline on Sinemet. In a double-blind protocol using CR4-Sinemet in 20 stable PD patients, CR4-Sinemet was given twice daily and compared with Sinemet given four times daily. Patients remained stable without improvement or deterioration when the long-acting drug was substituted at 50% frequency. Plasma levodopa levels with CR4-Sinemet were smoother than with Sinemet. Although some patients receiving CR4-Sinemet found they functioned more slowly in the morning, the easier dosing schedule and improved amount of "on" time in fluctuators suggest that this formulation may become increasingly useful in managing PD.

International (NL-UK) double-blind study of Sinemet CR and standard Sinemet (25/100) in 170 patients with fluctuating Parkinson's disease

“…One such preparation of levodopa and carbidopa, Sinemet CR (50 mg carbidopa, 200 mg levodopa), has proven successful at ameliorating motor fluctuations [6,17] and, importantly, has been shown to 236 be safe and as well tolerated as conventional formulations [1, 2, 4, 5,7, 9-11, 14, 16, 18, 19], The clinical efficacy of Sinemet CR has been found to be superior to that of the standard preparation of Sinemet (Sinemet STD; 25 mg carbidopa, 100 mg levodopa) in both open and double blind preliminary studies [1,2,4,5,7,10,11,14,16,18,19].…”

Soluble and controlled-release preparations of levodopa: do we really need them?

“…The lower bioavailability of controlled-release formulations depends on less efficient intestinal absorption of the drug or a greater first-pass metabolic decarboxylation of levodopa resulting from the slow drug release from the tablet matrix. Standard levodopa preparations have a half-life of less than 2 h, whereas controlled-release preparations have a half-life of more than 2 h. The longer half-life of controlledrelease levodopa, and the consequent more stable plasma levodopa levels [7,16] should increase the time between levodopa doses and consequently decrease the number of daily drug intakes.…”

Current Status of Symptomatic Medical Therapy in Parkinson’s Disease

“…Controlled-release formulations were tested in the 1980s to treat fluctuations in response, and the fourth formulation, Sinemet CR4, was approved in the United States in 1991. [12][13][14][15] Levodopa has its drawbacks, however, which may relate to the pulsatile drug delivery. These include late complications such as motor fluctuations and dyskinesias.…”

“…HC is metabolized back to methionine via methylene tetrahydrofolate reductase (MTHFR) or to cysteine via other mechanisms. These enzymatic reactions occur in the presence of cofactors folate, vitamin B 12 , and vitamin B 6 . Deficiency of any of these could lead to elevated HC levels.…”