Quantifying the short term effect of ropinirole CR on me
 

I've been trying to understand the effect that the drugs I take for PD have on me.

I've posted previously on the short term effect of Stalevo:

http://neurotalk.psychcentral.com/thread183360.html

This time I report on controlled release ropinirole. (I used a generic. The main brand is Requip XL.)

The short duration of effect for levodopa based drugs make it possible to measure their effect using the side-to-side tap test method, taking the test every 10 to 15 minutes over a 5 hour period. For longer lasting drugs like controlled release ropinirole durations are longer, at least 24 hours, and the tap test approach requires more commitment than I'm prepared to devote to its measurement.

As an alternative I used the following technique: under the control of an Arduino micro-controller, an accelerometer measures the magnitude of the acceleration of the back of the head every tenth of a second and writes the average every minute to a micro-SD card. The data is then moved to a laptop where it can be analysed.

The drawback of this approach it that the activities you do affect the results. For instance, walking and sleeping are likely to have different traces even when dopamine levels are the same.

Data was recorded for 24 hours. I started the test 30 minutes after waking, 23 hours after the previous dose of ropinirole and 12 hours after the last dose of Stalevo. I waited 4 hours before taking 8mg ropinirole at time 0. I took no other drugs during the test. I slept in a chair (so as to keep the accelerometer free to move) between approximately 750 minutes and 1170 minutes after the dose.

Attachment 9027

There is a lot of noise in the readings. But, very tentatively, I suggest the following periods:

Time in minutes from dose.

-240 - 0: left over effect from the previous day's dose, plus my own dopamine production mean I do quite well.

0: reserves run out leaving me "off", leading to me to take the dose then.

0 - 450: slow increase.

500 - 750: plateau

750 - 1170: less movement during sleep, but increasing as the night progresses. It would probably still be on the plateau if I were awake.

1170 - end: more active as I wait for the results.

Obviously, more work needs to be done to validate this approach, but the results share some common features with those found using the plasma levels approach reported by Malewar et al. [1, Fig 4].

Reference:

[1] "Controlled Release of Ropinirole Hydrochloride from a Multiple Barrier Layer Tablet Dosage Form: Effect of Polymer Type on Pharmacokinetics and IVIVC"
Nikhil Malewar1 , Makarand Avachat1, Varsha Pokharkar2 and Shirish Kulkarni
AAPS PharmSciTech
An Official Journal of the American Association of Pharmaceutical Scientists
2013
http://link.springer.com/article/10..../fulltext.html

John

It is worth taking a deeper look at Fig 4 of the paper by Malewar et al. mentioned above. Don't worry about the two graphs (one of Requip XL and one of a different formulation of ropinirole CR), what follows applies to both.

On an initial dose the graph shows:
Time (hr)
0-5, plasma levels rising linearly from 0
5-15, plateau
15-32, plasma levels falling linearly to 0

Roughly 1/6th of the area under the curve is in the second day. The consequence of this is that, assuming doses are taken every 24hr, levels will build slightly over a few days. Roughly speaking, we can see this effect by cutting out the area beyond 24 hours and adding it to the initial section of the graph. So, at the start of subsequent days, when we take a pill at time 0 (which contributes nothing at time 0) we get all our benefit from the previous day's pill, giving a total approximately half that of the plateau. (It's a pity that for those taking levodopa as well, this coincides with the time levodopa levels are at their lowest.) So, if one pill is taken per day, on subsequent days there is a swing of about 50% from highest to lowest concentrations.

We can reduce variability by halving the dose, but taking it twice as often. (This should not be done by cutting a pill in half.)

John