[johnt]

Quantifying the short term effect of Stalevo on me

The attached graph shows the pharmacodynamics of a single (75 mg levodopa) Stalevo pill on me.

dynamics.png

Side-to-side tap test results (high is good):

Baseline (4 readings).
Mean left = 13.03 taps, right = 11.84 taps

After taking the pill (17 readings)
Mean left = 21.34, right = 18.36
Max left = 29.24, right = 24.23
First minor effect seen 30 minutes after swallowing the pill.
First major effect seen after 50 minutes.
Peak reached after 90 minutes.
Back to baseline results after 165 minutes.
Correlation left/right = 0.966
The area under the curve and above the baseline (gives a measure of the drug's total effect) = 2438 taps.

Details.

To reduce the effect of my previous drug intake on the result, I started this experiment "off". This is difficult for me because I take some long acting medication, Requip XL and rasagiline. I was off these for 36 hours before starting. I was also off my fast acting medication, Stalevo, for 14 hours. This meant that, although not all the drugs had been washed out of my system, whatever was left was unlikely to have a large confounding effect on the result. Meals can also affect the results: I ate a large meal 7 hours before starting and ate half a slice of bread with the pill. I drunk some water on several occassions. Similarly, exercise can also affect the result, I was at my desk for almost the whole 3 hours 35 minutes that I ran the test.

To measure the results I used my online, side-to-side tap test program:
http://www.parkinsonsmeasurement.org...eToSideTap.htm
This measures the number of times you can type q followed by p in 30 seconds using just the index finger of one hand. It is done separately for each hand. I took 21 readings, one every 10 minutes, except there was 15 minutes between my last reading before taking the pill and my first reading after taking the pill and 15 minutes between each of the last three readings.

In the table below times are in minutes. Negative times represent the period before the drug was taken. LH and RH denote the left and right hand, respectively. Taps refers to the number of q,p cycles done in 30 seconds using just the index finger of one hand.

Time,LH_Taps,RH_Taps
-35,13.37,11.48
-25,12.81,11.81
-15,12.95,11.94
-5,12.98,12.11
10,12.92,12.85
20,13.85,11.41
30,15.98,12.53
40,15.05,12.41
50,18.42,17.55
60,26.43,21.55
70,27.41,21.87
80,25.53,22.84
90,29.24,24.23
100,28.23,24.18
110,26.75,24.08
120,26.08,21.97
130,23.60,21.81
140,22.32,17.17
150,17.38,17.10
165,12.17,9.34
180,13.02,10.12

John

[Songfellow]

John, am I reading it right? A higher time is worse, right? So, the way I read it (which must be wrong) is that you start with a low time (good) and after an hour or so you get a high time (bad).

It may just be my PD fog because you said you started "off".

Steve

[johnt]

Songfellow,

My apologies for not being clearer.

I'm measuring the number of taps made in 30 seconds, so the higher the better. Therefore, as the graph goes up my condition is improving.

It's worth noting that even my best score is lower than any healthy person who has taken the test.

John

[Songfellow]

John,

Oh, no problem at all. In the future you might want to re-label your Y-axis a bit by adding something like "Number of Hits" or similar.

It is really nice seeing the scientific method applied with your graph being a real tool for communication. It helps the PD community engage in rational fact-based conversations. We can start deciding which drugs, etc, are helpful and which aren't.

You've taken a real step by making your test available on the Internet.

What do you think of this idea? I'm just floating it out here as a "straw man" to start conversation.

If you (or any other member) have access to a suitable computer pen graphics tablet and are really sincere about running some studies using the 3LT method (and will report your results back to this group), just private message me your email address and I'll send you the software, instructions, etc.

I really would like to start calibrating these 2 test methods together.

Nice job!

Steve

[soccertese]

Originally Posted by Songfellow

John,

Oh, no problem at all. In the future you might want to re-label your Y-axis a bit by adding something like "Number of Hits" or similar.

It is really nice seeing the scientific method applied with your graph being a real tool for communication. It helps the PD community engage in rational fact-based conversations. We can start deciding which drugs, etc, are helpful and which aren't.

You've taken a real step by making your test available on the Internet.

What do you think of this idea? I'm just floating it out here as a "straw man" to start conversation.

If you (or any other member) have access to a suitable computer pen graphics tablet and are really sincere about running some studies using the 3LT method (and will report your results back to this group), just private message me your email address and I'll send you the software, instructions, etc.

I really would like to start calibrating these 2 test methods together.

Nice job!

Steve

steve,
i for one don't need these tests to have a rational discussion about pd drugs and which ones work for me. and how well a drug works isn't the primary consideration for Y0PD'ers, otherwise most everyone would be put on sinemet.
maybe that wasn't what you meant.

[Songfellow]

In my humble opinion (IMHO), having tests that give numerically measurable results offer us the opportunity to make improvements and to see things going wrong before they actually go wrong.

For example, if I'm feeling really good then I have no need to have my blood pressure checked. A blood pressure device would be a waste of money.

But, if I do have it checked then there is an instrument available to explain that the reason I suddenly passed out is that my blood pressure got too low. Having a numerical history of what was normal for me suddenly becomes very important.

Yes, everyone might be put on Sinemet (not likely because it doesn't work for everyone) but I, for one, really enjoyed being able to fine tune my dosage over the past many years because I had a reliable statistic to tell me that it was optimum.

Thanks for your input!

Steve

[soccertese]

steve, you won me over!

just curious,
what meds did you fine tune and what was the outcome?
that intrigues me, i stopped taking selegilene because it raised my BP and honestly, i can't notice any difference, might even feel better and i guess it would be interesting to quantify that. but one can assume that if you can't "feel" the difference, then who cares if the measurements show one?

and of course it would be useful when switching generics, to quantify the benefit so you can have some evidence that one generic might be worse than another and complain to your insurance company or the FDA. I'm on a roll here!

it also seems a lot of azilect is being prescribed to those just diagnosed, it WOULD be interesting to see if it really made any difference in a specific individual. of course, i assume one reason a lot of RX's are being written is the potential neuroprotective benefit.


and having a common measurement to compare the benefit of a supplement(s) would be very useful. how much do those pads cost?

[johnt]

Steve,

I suggest we do a trial trail before anyone goes out and buys a graphics tablet. (I have one already, a "Trust". Is this likely to come up to spec?) If that goes well, let's get other people involved.

soccertese,

You raise the issue of Azilect (rasagiline). It has no apparent effect on me. BUT ...

The literature reports that 1 mg of rasagiline is theraputically equivalent to 100 mg levodopa [1]. Now, 100 mg of levodopa (taken as part of Sinemet or Stalevo) would have a very noticeable effect on me.

How can those two positions be reconciled?

My hunch is that it's because the duration of rasagiline's effectiveness is so much longer. It is normal to take one rasagiline 1 mg pill per day, while Sinemet and Stalevo are often taken at 3 hourly intervals. So to get the same AOC (area under the curve) you need only one eighth (3 divided by 24) of the average impact. A dose of 12.5 mg of levodopa might not be noticed by many people, especially given all the other medications that we take. But that doesn't mean that the rasagiline is not "working".

(Interestingly, the difference is not in the main caused by rasagiline having a longer half life. An NIH archives document [2] states:

"Its mean steady-state half life is 3 hours but there is no correlation of pharmacokinetics with its pharmacological effect because of its irreversible inhibition of MAO-B."

I take that to mean that rasagiline comes in, does its job and departs, but that its effect carries on far longer:
"Studies in healthy subjects and in Parkinson's disease patients have shown that rasagiline inhibits platelet MAO-B irreversibly. The inhibition lasts at least 1 week after last dose." [2])

References

[1] "Levodopa Dose Equivalency", Claire Smith, 2010.
http://www.birmingham.ac.uk/Document...hLEDReview.pdf

[2] http://dailymed.nlm.nih.gov/dailymed...rchiveid=10668

John

[Dan Murphy]

Thank you for the time you spent on this study. It is very helpful for me.

[soccertese]

Originally Posted by johnt

Steve,

I suggest we do a trial trail before anyone goes out and buys a graphics tablet. (I have one already, a "Trust". Is this likely to come up to spec?) If that goes well, let's get other people involved.

soccertese,

You raise the issue of Azilect (rasagiline). It has no apparent effect on me. BUT ...

The literature reports that 1 mg of rasagiline is theraputically equivalent to 100 mg levodopa [1]. Now, 100 mg of levodopa (taken as part of Sinemet or Stalevo) would have a very noticeable effect on me.

How can those two positions be reconciled?

My hunch is that it's because the duration of rasagiline's effectiveness is so much longer. It is normal to take one rasagiline 1 mg pill per day, while Sinemet and Stalevo are often taken at 3 hourly intervals. So to get the same AOC (area under the curve) you need only one eighth (3 divided by 24) of the average impact. A dose of 12.5 mg of levodopa might not be noticed by many people, especially given all the other medications that we take. But that doesn't mean that the rasagiline is not "working".

(Interestingly, the difference is not in the main caused by rasagiline having a longer half life. An NIH archives document [2] states:

"Its mean steady-state half life is 3 hours but there is no correlation of pharmacokinetics with its pharmacological effect because of its irreversible inhibition of MAO-B."

I take that to mean that rasagiline comes in, does its job and departs, but that its effect carries on far longer:
"Studies in healthy subjects and in Parkinson's disease patients have shown that rasagiline inhibits platelet MAO-B irreversibly. The inhibition lasts at least 1 week after last dose." [2])

References

[1] "Levodopa Dose Equivalency", Claire Smith, 2010.
http://www.birmingham.ac.uk/Document...hLEDReview.pdf

[2] http://dailymed.nlm.nih.gov/dailymed...rchiveid=10668

John

your're right, it binds to MAO-B and inactivates it, how long it takes to replace that inactivated MAO-B obviously is more than a day.
i also mentioned that i stopped taking selegilene, an older irreversible mao-b inhibitor, and noticed no increase in pd symptoms after 2 weeks. so there must be cases in advanced pd'ers where azilect shows no improvement also.

and most people are starting azilect by itself.