Useful
 

Thanks for this thread Johnt, a good resource.

I've written a very small app that calculates the LEDs of your drugs and totals them to get your levodopa equivalent daily dose (LEDD). It runs directly from the web page, so there's nothing to install. It can be found on my web-site at:

http://www.parkinsonsmeasurement.org...valentDose.htm

John

We left this thread with an app that calculated LEDs. This was, as far as it went, fine, but it didn't capture the time nature of the drugs. So, for instance, 1mg of rasagiline has a LED of 100mg, which by definition is the same as 100mg levodopa/carbidopa. But, the rasagiline is effective for the whole 24hr period, whereas the levodopa is effective for, perhaps, 4 hours: in the end they give the same "volume", but one is like a long-term trickle, whereas the other is like a short-term flood. I've written a new app which, in part, addresses this issue, by looking at the pharmacokinetics (what the body does to the drug) of the situation. This leaves unaddressed, and needing to be done, an app to look at the pharmacodynamics (what the drug does to the body) of PD drug regimens.

My app can be run directly, there's nothing to download or install, from:

http://www.parkinsonsmeasurement.org...cokinetics.htm

(I've only added a few drugs. I will add others later. I've also not created a link from the web site's home page to the app. I'll add that when things are stable.)

This is a screen shot showing the app's output given my PD drug regimen.

Attachment 9350

Please play with the app and let me have your comments.

My thanks go to Ron Strong and Angela Wensley with whom I've been in contact with on this subject. A few weeks ago Angela posted on her Excel-approach to PD pharmacokinetics see:

http://neurotalk.psychcentral.com/thread218873-2.html

John

Very good, can you add sinemet CR?

*administrative edit as per NeuroTalk Guidelines*
The difference in approach is that my data is manly derived from digitised blood plasma charts whereas Johns are pharmokinetic data.

I would say comparing rasagiline with levodopa is like comparing butter to salt, in that they don't do the same thing. But it is interesting nevertheless

Thanks Ron.

I'll update the app to include Sinemet CR as soon as I can find some consistent data. Angela as been so kind as to forward to me some papers on the subject.

I take your point that rasagiline and levodopa are different. But, they are both involved in the same battle: increasing dopamine levels in the brain. Levodopa leads to dopamine being created and rasagiline reduces the amount of dopamine that is lost. Either route can lead to the same amount of dopamine being present in the brain. If you could go on adding to the rasagiline dose and get increasing levels of dopamine preserved it would be a wonder drug. Unfortunately, it does not give better results for doses above 1mg/day - presumably it has done its job as a MAO-B inhibitor and there is no more MAO-B to inhibit.

John

My app does much the same job but it calculate the sum effect for correlating with other reading.I'd say the rasagiline never has any effect (but I'll keep on taking it I can't prove otherwise.

Thanks by the way for you hard work on this

my app is at model.strong.org.uk
Register and I will approve

Wendy writes:

"I'd like to use Mirapex in the graph if I can. Its TMAX is 2 hrs, THALF is 8-12 hrs. depending on age, and the conversion factor is 100. ... How do I figure out the CMAX?"
http://www.neurotalk.org/parkinson-s...evadopa-2.html

Unfortunately my program does not include Mirapex. But, given the interest shown I'll extend it to include this drug and a few other common ones too. The difficulty is not in the programming, but rather finding reliable sources of the pharmacokinetic parameters on which the model is based. This will take some time to do, so in the meantime a work-around is required. I will go into a lot of detail, because I think it important that anyone using this tool understands how it works.

The simplest, but least accurate way, is to take a similar drug and use that as a proxy. In this case, ropinirole is a possible alternative. The conversion factor for levodopa is 1, for ropinirole it is 20 and for Mirapex it is 100. To balance the books you can select ropinirole and give it a dose of 5 times more than the Mirapex dose. So, a 1mg dose of Mirapex is entered as a 5mg dose of ropinirole. If you enter these values into the grid and also enter a line showing a dose of 100mg levodopa, you will find that as expected the two doses have almost the same area under the curve (AUC). The problem is that the program has chosen a TMAX of 90 minutes (when you wanted 120) and a THALF of 360 minutes (when you wanted 480-720 minutes).

A more accurate way to work around the problem is to change the default values of TMAX and THALF to those that you want, but initially keep the default value of CMAX (5.59). Putting TMAX to 120 and THALF to 600, and pressing Calculate gives an AUC of 20602, which is wrong: it should equal 14686 (because 5mg of ropinirole is equivalent to 100mg of levodopa, and LED is based on equal AUCs). The final step is to by trial and error adjust the CMAX value to get the correct AUC: there is a linear relationship between CMAX and AUC). CMAX=4 gives AUC=14742, which is close enough.

Please remember that this is just a mathematical model, which makes numerous assumptions, which is based on data which is inexact, and which does not take into account endogenous dopamine production and storage. Also, it is one step removed from what we really want to know, which is the pharmacodynamic impact of our drug regimen: how, for instance, does our bradykinesia change during the day.

My efforts are going into "dynamic dosing": producing electronic tools that detect when you're nearing an "off" with enough notice for a dose taken now to kick-in before the "off" happens.

John

Looking for the Mirapex Update
 

John, I'm new to the forum but have precisely the issue discussed here. In addition to dyskinesia from too much Levodopa, I am experiencing compulsions to spend $$ and drive fast.

My meds at this moment include Rytary ER, Mirapex ER, Rasagaline, Donepezil, Levothyroxine and Escitalopram. I understand that only the first three impact my Levodopa levels but include the rest for completeness.

Questions:

1. Do you have a version of your app that includes Mirapex ER?

2. Does your app support the ER versions of Rytary and Mirapex in addition to the standard versions?

Working with my Neuro Doc, I am drawing down and eventually quitting my Mirapex, and eliminating my Rasagaline altogether. My intention is to accurately display the total Levodopa amount over time so I can plan the best way to find my correct types and amounts of meds.

Thanks for a wonderful thread and an excellent app to work with!

Brian

Ron, is your model still available? When I click on the link, all I get is a blank screen.

I'm registered in the group - what else do I need to do?

Brian