The brand name formulation of the anti-Parkinson’s medication most commonly used in the United States, a combination of levodopa and car-bidopa that is manufactured by Du Pont. About 80 percent of people with Parkinson’s disease use this drug or one of its generic counterparts. In the early stages of Parkinson’s, Sinemet typically is so effective that symptoms entirely disappear. As the disease progresses, however, Sinemet’s effectiveness diminishes. Although increasing the drug’s dosage can prolong its effectiveness, it also increases its side effects, which can include nausea, dyskinesias, and dystonia (extreme muscle rigidity).
Sinemet, or levodopa/carbidopa, is generally preferred to levodopa alone because the carbidopa helps to mitigate the more distressing side effects of levodopa (primarily nausea and a sense of queasi-ness). The dosage must introduce enough levodopa into the body to produce a level sufficient to pass the blood-brain barrier, enters the brain, and there supply enough dopamine to meet the brain’s needs. After being absorbed into the bloodstream, levodopa is subject to rapid peripheral metabolism through the actions of the enzyme dopa dEcar-boxylasE (DDC). The high levels of peripheral dopamine cause moderate to severe nausea, light-headedness, and other side effects.
Carbidopa is a dopa decarboxylasE inhibitor (DDCI), which slows peripheral levodopa metabolism. Taking the proper amount of carbidopa (usually 50 mg to 75 mg per day is sufficient for most people) both avoids the side effects of nausea and lightheadedness and increases the amount of levodopa that reaches the brain where brain DDC helps metabolize the levodopa to dopamine for use by brain neurons. As the blood-brain barrier prevents dopamine in the brain from passing back into peripheral circulation, high levels of dopamine in the brain have no effect on functions elsewhere in the body. As levodopa depends on active transport from the gut, taking it with protein, which competes for the same transporters, significantly limits the amount of levodopa that can be absorbed. For this reason, most physicians recommend taking levodopa on an empty stomach (at least an hour before or two hours after eating) to avoid dietary protein causing variations in the amount of levodopa absorbed. This is particularly important in people with more advanced Parkinson’s disease who have clear motor fluctuations (frequent medication wearing off or dyskinesias). Many people with advanced disease note sensitivity to dietary protein even when they have taken steps to take Sinemet only well away from meal times.
Sinemet is available in tablets of varying strengths, with the 10/100 tablets seldom being used, except in patients taking eight or more tablets per day, due to the risk of their containing insufficient carbidopa to prevent the peripheral conversion of levodopa and the attendant side effects. controlled rElEasE (Sinemet CR) tablets are formulated to dissolve slowly in the digestive system and enter the bloodstream in a controlled fashion over time; ideally this provides more prolonged and smoother levels of levodopa, but in practice the long digestion makes absorption of the levodopa in Sinemet CR very variable and unreliable. Regular release Sinemet also can function as a rescue drug, since it often reaches therapeutic levels in about a half hour; Sinemet CR commonly takes well over an hour to kick in. A formulation that combines carbidopa, levodopa, and enta-capone in one pill should be on the market by late 2003, which provides the reliability and fast onset of regular release Sinemet with an extended duration of effect.
Generic formulations produced by other manufacturers include the brand names Atamet and Laradopa. Some people with Parkinson’s report that generic products are not as effective as the Sinemet brand name product. This is likely because formulation and manufacturing processes can affect how rapidly and completely the drugs dissolve and absorb into the bloodstream, and switching from one brand to another can change the level of levodopa that reaches the brain. Generally, clinicians recommend staying with the same brand, whether Sinemet or generic.
Although most people experience relief of most symptoms with the first dose, it can take several weeks to get the dosage to the desired therapeutic level. Dosing depends on symptoms and response, and it changes as the Parkinson’s progresses. The typical starting point is to take the prescribed dose of the regular release formula three or four times a day or take Sinemet CR, the extended release formula, twice daily. However, doctors may recommend taking the drug less or more frequently, depending on symptoms. As the course of Parkinson’s disease is highly variable among individuals, each person must work closely with the doctor to achieve balance between therapeutic benefit and undesired side effects. The potential drug interactions with levodopa, Sinemet’s therapeutic ingredient, are extensive; they are discussed in the levodopa entry.