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Novel Formulation of Levodopa May Ease Parkinsonís Symptoms with Fewer Pills

People with Parkinson’s disease (PD) who took a new formulation of levodopa tablets three times a day had more constant levels of the drug in their systems than those who took standard immediate-release levodopa four or five times a day, according to a new study in the journal Movement Disorders. The study also found that the new drug worked equally as well as optimized doses of levodopa. 

Levodopa remains the gold-standard drug used to treat the motor symptoms of Parkinson’s disease. When Parkinson’s advances, people may need to take levodopa four or more times a day to control PD symptoms. Even with so many doses, the levels of levodopa in the system can drop, causing a worsening of motor symptoms as the drug “wears off.”

Recently, scientists developed a novel form of sustained-release levodopa, which they hope may reduce fluctuations in levodopa levels. Compared with standard levodopa, the new form called XP21279 is absorbed throughout the intestines (instead of only in the upper part of the small intestines) and is a “slow release” formulation, meaning it is absorbed into the body from the intestines over a longer period of time instead of all at once. This means it could be taken only three times daily instead of four or more.

Researchers led by Peter LeWitt, M.D., at Henry Ford Hospital and Wayne State University School of Medicine, in Michigan, compared effects of XP21279 with those of standard immediate-release levodopa. In this double-blinded study, 28 people with mid-stage PD were randomly selected to receive one of the drugs for two weeks: either XP21279 three times a day or immediate release levodopa four or five times a day. Then, each person switched groups and received the other drug/dose for two weeks. 

At the end of each two-week period, Dr. LeWitt and his colleagues compared the average “off time” for each group with off times at the beginning of the study (baseline). They also examined how levels of the drugs in the blood fluctuated throughout the day.


  • Participants reported that off time was cut in half just by improving the way they took standard levodopa (adjusting timing and dosages).
  • When participants took the new formulation of levodopa, they experienced a very similar reduction in off time as with optimized standard levodopa, but were able to achieve this taking fewer doses.
  • In both groups, blood levels of levodopa were much more consistent throughout the day with the newer formulation of levodopa.

What Does It Mean?

Levodopa treatment is still the gold-standard treatment for PD. However, over time, people with PD who take the drug may experience off times, which can be very frustrating. Therefore, scientists are actively searching for new forms of levodopa or other drugs that can reduce off time. Evidence suggests that stabilizing the levels of levodopa in a person’s blood could be one way of doing so.

Compared with standard release levodopa, XP21279 did provide more continuous levels of levodopa in the bloodstream. Contrary to the researchers’ expectations, however, this did not result in significantly reduced off times. This may be because four people in the study failed to follow the directions about taking their medication with food, and subsequently had very poor results. Because the study is small, such problems can have large effects on the data. Thus, more research will be needed to establish whether or not the new drug can actually help reduce off times.  Nevertheless, this experimental drug was able to achieve similar effectiveness as standard, immediate-release levodopa.

In the meantime, this study does suggest that XP21279 may be an additional useful tool to the arsenal of medications that may reduce off time. However, XP21279 is still in the experimental stages and it must be studied further before it can be approved by the US Food and Drug Administration (FDA) for the treatment of PD.

An interesting result of this study was that almost all the participants, who had PD for an average of almost nine years, saw great benefit simply by having their medications optimized (e.g., dosages and timing improved).  This means that before the study, many participants were undertreated and may have benefitted during the trial, from seeing experts in the field of Parkinson’s, called movement disorder specialists.  

And this illustrates again why PDF recommends seeing a specialist to help treat and manage the symptoms of Parkinson’s disease. 

Learn More

Do you have questions about medications or specialists in the field of Parkinson's? Find answers or a PD specialist near you by calling us at (800) 457-6676 or or use our free resources below.

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Reference: Lewitt PA, Huff FJ, Hauser RA, Chen D, Lissin D, Zomorodi K, Cundy KC (2014) Double-blind study of the actively transported levodopa prodrug XP21279 in Parkinson's disease. Mov Disord 29:75–82.  DOI: 10.1002/mds.25742

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Source Date: Mar 20 2014