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Post of the Week: Sinemet preparations


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#1 Dr. Fernandez

Dr. Fernandez

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Posted 19 December 2009 - 05:58 PM

Why are there different forms of carbidopa/levodopa? Are they really different from each other?

Carbidopa/levodopa is now available in 4 forms: immediate-release, orally-disintegrating, sustained-release tablets, and as an intenstinal gel (marketed as Duodopa in Europe). Ideally, levodopa is best taken at least 30 minutes before or one to two hours after meals to decrease the competition with amino acids for absorption across the small intestine. Medication can be taken with a small non-protein snack if amino acid competition is a concern and nausea is a problem.

Carbidopa/levodopa in immediate-release form is available in 10/100, 25/100, or 25/250 mg strengths. Dosing is typically initiated at one 25/100 mg tablet three times daily and increased by one pill as necessary until a clinical response is achieved. The recommended maximum doses are 200 mg carbidopa and 2000 mg levodopa per day. Ocassionally, the immediate-release form is used to make a liquid preparation for Parkinson’s disease patients with significant motor fluctuations by mixing 10 tablets with ½ teaspoonof ascorbic acid crystals and 1000mL distilled water. This preparation allows small frequent dosing with the goal of relieving wearing off symptoms without causing or worsening peak-dose dyskinesias.

Parcopa is an immediate-release, orally-disintegrating form of carbidopa/levodopa available in the same dose combinations as the standard tablets. It dissolves underneath the tongue without requiring water. But unlike the orally-disintegrating selegiline, it still needs to go through the gut and to get absorbed. Therefore, its onset of action is not much faster than the immediate-release carbidopa/levodopa. Parcopa contains phenylalanine, 3.4 mg in the 10/100 mg and 25/100 mg strengths, and 8.4 mg in the 25/250 mg tablets.

Sustained-release carbidopa/levodopa is available in 25/100 mg and 50/200 mg strengths. The time it takes to reach peak efficacy is slower than the immediate-release, taking about 2-3 hours. Thus most patients who have been exposed to the immediate release form do not like the controlled release form because they don’t feel the “kick start” that they usually do when they take the immediate-release formulation.The initial recommended dose is 50/200 mg twice daily, at least 6 hours apart. The dose can be increased every few days up to a “theoretical” maximum of 8 per day, with 4-8 hr intervals between administrations. Dose requirements of the controlled-release preparation are usually 10-25% higher than regular release levodopa owing to its decreased “bioavailability”. Absorption is altered by both the stomch acidity and the time it takes for the stomach to empty its contents and pass it on to the small intestines, which may be slower in elderly subjects or in the presence of food. Taking Sinemet CR with protein will also decrease absorption due to competition with amino acids for absorption from the small intestine. Sinemet CR should not be crushed or chewed, otherwise it functions like an immediate-release tablet.

Finally, carbidopa/levodopa can now be continuously infused in the intestine through a stomach tube. This continuous delivery of levodopa in the form of a liquid gel prevents and relieves motor fluctuations. It is only available in Europe at the time of this writing. There are a few centers in the in the United States that are offering this formulation but only as part of a research clinical trial. The ideal candidate for the cabidopa-levodopa intestinal gel formulation is a Parkinson’s disease patient experiencing significant motor fluctuations or dyskinesias despite the best efforts to optimize treatment.
Hubert H. Fernandez




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