Sinemet CR at 200/50 2x for total of 400 mg (actual quantity available due to CR form is about 350 mg). Taken at 5:00 AM. Followed at 6:00 AM by 750 mg creatine monohydrate as single capsule (NOW brand).

Results were noticeable and very positive by 6:30 AM and continued so until about 7:30 AM when an unmistakeable reversal was noted and a period OFF began and continued until approx noon. Additional sinemet scheduled at 9:00 AM had no obvious effect. The reversal at noon back to a normal ON state was normal as was the rest of the day.

Comment- I think this was a case of the uptake of sinemet from the small intetsine being blocked temporarily by the creatine, an amino acid. Sinemet (actually the levodopa portion) is moved from the gut into the bloodstream and then past the blood brain barrier by means of specialized transport molecules. These structures are sized to fit particular size ranges of amino acids and will not interact with others. Therefore some proteins (amino acids) will interefere while others will not. Also, the time it takes to clear one amino acid will impact the handling of a second amino acid.

I think that the initial dose of sinemet made a good start, but the addition of the creatine, while it initially gave a boost to my system, interfered with the later dose of sinemet with the resulting slump as supplies of both dwindled with the mutual competition. By noon the creatine levels had dropped enough for the system to right itself.

The creatine did have a very beneficial initial effect and is worth some effort to determine if there is a way to use it. Earlier I had tryed taking it at the same time as the sinemet with ubsatisfactory results, as might be expected. I had also tried taking the creatine at bedtime. This had the unfortunate effect of shifting the considerable stimulant effect and making sleep impossible as well as interefering with the morning dose of sinemet.

One problem is my need to space sinemet at intervals of approx two hours and the four hour window that creatine is present to interfere. A patient with a longer spacing might be able to postpone the next sinemet longer and allow the creatine to clear.

Another possible approach might be to take a large dose of sinemet first thing in the morning and allow more time for it to get started and to take the creatine at that time. Then coast on the first wave until the creatine starts to wain and hope to hit the "sweet spot" of the next large dose of sinemet.

Working out this problem may be more important than is obvious due to the fact that several potentially valuable compounds may pose similar problems (carnitine and tyrosine, for example).