Greetings.  The following is a bit long and, no doubt, tedious, but I'm 
interested in your thoughts.  I also don't know if the graphic (a small jpeg 
file) will go through. If not, the rest won't make as much sense.  You'll 
want to have the graphic displayed while reading the rest.

Roger

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PLEASE NOTE!!
What follows is for discussion purposes only.  I am not a medical 
professional and I am in no way suggesting that the methodology or results 
that I will be presenting be adopted by anyone else to replace or supplement 
your own medication regimen.  Nor am I suggesting that my findings will work 
for others in the same way they worked for me.  I simply wish to share these 
findings as a means to help others gain insight into the workings of certain 
medications and, through your comments, a better understanding of (and 
corrections to) my own ways of thinking this through.

Background: I am a 59 year old PWP, male, diagnosed almost 13 years ago.  I 
am still (thank goodness) petty high-functioning and lead a fairly active, 
“normal” life.  My meds have changed over the years.   I am currently taking 
only generic versions of Stalevo 150 and Sinemet 25/100 for managing my PD. 
I had been taking one of each pill 5 times daily, roughly 2.5 to 3 hours 
apart.  I found that I could discontinue my before-bedtime dose with 
insignificant effect on my ability to function.  (Besides, I had fewer 
digestive problems at night).  Now, I take one pill of each, 4 times a day, 
roughly 3.5 hours apart.  I adjust this interval slightly and may add a 
fifth dose in the evening if I’ve had a more “off” day or have simply been 
up and active more hours that particular day (got up at 6 am instead of 8, 
for example).

In recent months, I (and my wife) have noticed some increase in my 
dyskinesias, especially excess movement of my head.  After some time, my 
neck was becoming stiff, my head movements were becoming more restricted, my 
upper back was constantly tense and painful, I was having problems with 
pinched nerves in my upper back (from the tension), etc.

I started to look at the timing of the medications I’m taking, not just the 
dosing intervals, but also how the drugs enter the bloodstream and brain. 
I used the data I could find to model the drug blood concentration 
mathematically.  I created models for the Stalevo 150, full Sinemet 25/100 
pill and half Sinemet pill.  I then put these models onto an Excel 
spreadsheet and juggled them until I was able to get a fairly “flat” curve, 
representing a more consistent drug concentration in the blood.

From the online data that I was able to find on the pharmacology of these 
two drugs, I found:
Sinemet:
Time to maximum concentration: 30 minutes
“Half life”: 1 ½  hours
Max concentration: 2 units *

Stalevo:
Time to max concentration: 2 hours
Half life: 2 ½  hours
Max concentration: 3 units*

* The max concentration units are arbitrarily assigned.  As the ratio of 
levodopa between Stalevo and Sinemet is 3:2, I just stuck with these 
numbers.  The graphs show *relative* results so more specificity is not 
needed.

Disclaimer:  I am not going to pretend that the numbers I found are 
definitive, nor that the mathematical modeling (using mostly exponential 
characteristics for both rise and fall of blood concentrations from each 
drug) are accurate. I do believe they illustrate trends in a reasonable 
manner.

Graphs:
The first graph shows a single line representing the blood concentration of 
levodopa as a function of time.  Time is measured in hours from when the 
first dose is taken.  In this case, the graph shows the concentration that 
results from taking one of each pill, together, at 3 to 3 ½ hour intervals 
("standard" dosage).

The second graph shows a modified dosing.  The fainter lines that peak at 1 
unit are half pills of Sinemet.  The fainter line that peaks at 2 units is a 
whole pill of Sinemet.  The dark lines that peak at 3 units are the Stalevo 
150s.  The heavy line at the top is the sum of the Stalevo and Sinemets.

Discussion and Observations:
The top graph (“standard” dosing) has a periodic characteristic (expected). 
During each period, there appears to be roughly 1 ½ hours during which the 
blood concentration of levodopa is reasonably consistent.  Between these 
times, there’s a 1 ½ hour period where the concentration nose dives then 
climbs back as the next dose kicks in.  These represent “on” and “off” 
periods during the day.

The top graph also shows that the max concentration is between 3 and 4 units 
for the first period, then jumps to 5.5 units and continues to rise to 6+ 
units during the fourth period, indicating that the levodopa continues to 
accumulate throughout the day.  Comparing to my own experience, it usually 
takes me 2+ hours to “get going” in the morning.  As the day goes on, my 
dyskinesias get worse the worst time being in the evening hours, 
corresponding to the fourth period of the graph

The modified dosing used for the lower graph shows a flatter concentration 
curve: from 30 minutes after the first dose and for the next 11+ hours, the 
concentration of levodopa stays between 4.3 and 5.4 units (approx.), so it 
is more consistent and a bit lower, on average, than the “standard” dosing. 
My experience doing this modified dosing is consistent with the graph: 
faster response in the morning, fewer tremors and less stiffness during the 
day, no real “off” periods, much less dyskinesias and those I had were less 
noticeable.  The tension and pain in my back and shoulders went away and I 
regained neck movement.

As shown in the lower graph, I ended up taking only 3 Stalevo 150 pills, 
along with 1 full and 11 half Sinemet pills, or 2 Stalevos and 6½ Sinemets 
versus the “standard” dosing of 4 Stalevos and 4 Sinemets.  For my case, I 
believe that my optimal concentration should be closer to 4 units.  I 
believe I can achieve this by eliminating 2 or 3 half sinemets and changing 
the timing some.

The obvious drawback of the modified dosing is that it requires taking pills 
(mostly half Sinemets) quite frequently and at very specific times during 
the day.  I think that, in some if not most cases, this inconvenience and 
discipline might not outweigh the benefits.

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