The plasma half-life of levodopa (taken with carbidopa) is only about 90 minutes. As I understand the issue, this presents us with a problem. In order to get a benefit from the drug, we need to take enough to raise levodopa levels above the therapeutic threshold. But, with such a short half-life, if we take just enough levodopa to get to the threshold, plasma levels will quickly drop below the threshold, leaving us with a very short "on". To get around this, we need to take larger amounts of C/L. In the early stages of the disease this does not cause much of a problem because the dopamine produced from the excess levodopa is stored in vesicles, and can be used as required to smooth dopamine levels. The problem comes when, as the disease progresses, the death of dopaminergic neurons means that not only is less endogenous dopamine produced, but the vesicular reservoirs are diminished. This eventually leads to the excess levodopa causing problems, particularly dyskinesia.

Optimal levodopa therapy is likely to require both immediate release levodopa to give an "on" quickly and a controlled drug delivery system with a long half-life to keep plasma levels just above the therapeutic threshold for as long as possible.

With this in mind, I've investigated the effect of taking C/L and entacapone in a gel. In my case, this involves first dissolving Stalevo in Vitamin C. Then mixing this with a gel (in my case Movicol, macrogol, polyethylene glycol, 3350) which I take for PD induced constipation.

The reasons for choosing macrogol are:

- I already take it;

- "Macrogols are also attached to biopharmaceutical drugs to slow down their degradation in the human body and increase their duration of action" [1]

- Macrol gets into the upper colon and may (I have no evidence for this) get more levodopa into a position where it may be absorbed.

I gave it a try.

Results

StalevoVitCMovicol.png

The results are compared with those from a test held on the next day using the same medication, but without the Movicol. The results from this have already been reported in another thread [2, Post #18].

The results come in pairs: first Stalevo + VitC + Movicol results and second the Stalevo + VitC results, which are in [].

Baseline (3 readings).
Mean left = 21.11 [22.26] taps, right = 17.71 [17.23] taps

After taking the pill until return to baseline (16 readings)
Mean left = 33.22[31.78], right = 25.31 [22.88]
Max left = 39.64 [37.69], right = 31.60 [28.56]
First major effect seen after 50 [50] minutes.
Peak reached after 140 [50] minutes.
Back to baseline results after 170 [150] minutes.
Correlation left/right = 0.968 [0.977]
The area under the curve and above the baseline (gives a measure of the drug's total effect) = 2761 [2125] taps. This figure can be interpreted as the number of extra taps that 75mg of Stalevo buys me.
Endogenous ratio 66% [72%]

Obviously little can be said definitively on the basis of a n=1 trail. But, the increase in the number of taps by about a quarter is encouraging, as is the approximately 20 minute increase in the "on" time.

I'll be grateful to hear from anyone who has looked at ways to get more out of levodopa.

References

[1] Macrogol - Wikipedia, the free encyclopedia

[2] Quantifying the short term effect of Stalevo on me

Appendix

The dose was 75mg/18.75mg/200mg (levodopa/carbidopa/entacapone) in Stalevo dissolved into 125ml of water with 1000mg effervescent Vitamin C and with one sachet (macrogol, 13.125g) of Moviocol mixed in.

Data was collected between 0510 and 0850 on 18th August using the side-to-side tap test program. At the start I was 670 minutes away from my previous Stalevo dose and 1270 minutes from the last dose of ropinirole and rasagiline. The last food eaten was 440 minutes before the dose.

Time,LH_Taps,RH_Taps
-20,21.67,17.83
-10,20.51,17.70
0,21.14,17.60
10,22.71,16.74
20,22.40,16.56
30,24.28,16.61
40,20.45,16.51
50,30.77,27.06
60,37.55,27.53
70,37.33,28.62
80,38.59,28.81
90,39.07,27.74
100,38.03,27.84
110,38.12,29.29
120,38.51,30.35
130,37.69,29.13
140,39.64,31.60
150,37.55,29.98
160,38.11,26.19
170,26.56,17.56
180,23.29,16.38
200,23.08,17.07

John