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?"
Inhaler for Levadopa

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

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

John, I am unable to come to a successful conclusion when using your by-minute app to find my Levodopa levels throughout my typical day.

Here are two scenarios I'd like to explore:

1. Initial Dosing of Parkinson's Meds

(3) capsules of Rytary ER @ 48.75mg Carbi, 195mg Levo
Total 146.5mg Carbi, 585mg Levo

The dose above is taken daily at 0600, 1030, 1500, 1930

(1) tablet Rasagaline 1mg at 0600 daily

(1) tablet MiraPex ER .75mg at 2230


2. Final Dosing After Removing Rasagaline and Mirapex

(3) capsules of Rytary ER @ 48.75mg Carbi, 195mg Levo
Total 146.5mg Carbi, 585mg Levo

The dose above is taken daily at 0600, 1030, 1500, 1930

Can you give me a reasonable result with your knowledge of how your app is set up??

Thanks - you brought great value to this discussion!

Brian

Brian,

Thank you for your interest in my levodopa equivalent pharmacokinetics graphing app.

As you've found, the tool is limited in the types of drug that it can cope with.

Post 18 in this thread gives a work-around for Mirapex. At its least accurate, you can approximate 1mg of Mirapex ER with 5mg of Requip XL.

Regarding Rytary, I show in a recent thread how to approximate one dose of Rytary with 4 doses of levodopa/carbidopa. See:

Approximating the pharmacokinetics of Rytary using IR C-L

So, you will need to fill in 18 lines, four for each of your four Rytary doses, plus one each for your Mirapex and rasagiline doses.

I've increased the number of doses that the program can deal with per day to 20.

John

I've added some new features to my app which draws a graph of the impact of your drug regimen on your levodopa levels:
- More drugs (but still not Rytary).
- An "on"/ "off" threshold estimator.
- A dyskinesia threshold estimator.
- Steady state as well as single dose solutions.

Parkinson's Disease Measurement: PwP, surveys, trials, analysis

See Post 13 in this thread for screen shots.

Please remember that this app is just a model based on inexact pharmacokinetic (what the body does to the drug) data, when what we really want to know is the pharmacodynamic (what the drug does to the body) impact of our regimen. But, it does help allow you to discuss your options with your doctors.

I believe that most of us can get more out of existing drugs than we do now if we and our doctors take the time to optimize our personal drug regimen.

John

Hello John,

Back in 1994 my chiropractor had me squeeze this hand held device that must have measured some subtle electric conductance. Before this he had thought that the tremor in my thumb and the pain in my elbow were simply essential tremor but when I saw that concerned look on his face and his immediate recommendation to see a neuro the gravity of my situation became ever more clear (Initially I thought my grip was pretty strong but thats' not what it was measuring). At the time my sx were subtle which is why I'm wondering if this device might also be useful for the applications you are suggesting for tweaking med dosages....A Good Parkinson’s Muscle-decline Measure Is Hand-grip Test, Study Says
Also, after reading some of your posts i am more carefully observing any sensation of tremor and stiffness ...breathing ease and anxiety as an indicator of when to take next dose. In the mornings I can take less but more frequently and more but less frequently towards the evening.

Kind Regards,
MD

Hello folks. Sorry for jumping in but I'm have a problem with my Sinemet dosing.

My current med list:


Azilect 1 mg tab. Take 1 tab in every morning at wake-up.

Amantadine, 100 mg tablet. Take 1/2 tab at 5:30 AM and 1/2 tab at 11:30 AM.

Sinemet 25-100 tab. Take 1 tab at 5:30 AM (wake-up) and 1 tab at 7:30 AM, 9:30 AM, 11:30 AM, 1:30 PM, 3:30 PM, 5:30 PM, 7:30 PM, 8:30PM and 9:30PM (bed time).

Sinemet ER 50-200 tablet (during the night). Take one tab at 9:00PM (bed time) and one tab at 1:30 AM.

Now here's the problem. I'm on a really tight dosage regimen during the day with the Sinemet 25-100. Taking a pill every two hours is a real challenge. I'm constantly missing timing of dosage and I end up on a 30-40 minute "off" or bouncing off the ceiling with over medicating. I don't know if I'm taking too much or not enough. The 25-100s are beginning to not offer relief of symptoms and if I take 1.5 tabs per 2 hours, I start to get overmedicated and then dyskinesia starts to cause problems. Any suggestions? Is 2 sinemet tabs every 4 hours the same as 1 tab every 2 hours. BTW, I did try Rytary and didn't work for me (side effects). Thank you.

taking 2 sinemet every 4 hrs probably won't help you and sounds like you'll get dyskinesia.
you need a constant concentration of C/L in your system and that happens with regular C/L by taking a smaller dose more often or adding an agonist and/or a drug such as azilect or entacapone which increases the half-life of l-dopa.

i imagine you have tried 50/200CR extended release C/L. You can take 1.5 200CR which would be 300mg L-D0PA but with reduced bioavailability compared to regular C/L you might not get dyskinesias and might get 2.5-3hrs. if you add some fat it will slow gastric emptying which is what you want to do with CR. a cracker with margarine, or 1/2 cup of cooked oatmeal with margarine, a fish oil capsule. it should kick in in about 90minutes. i try not to take 2 CR doses in a row since it can buildup in your stomach and you get too much l-dopa so my pattern is 100mg C/L, wait 60minutes then take 50mg C/L + 50/200CR. wait 2.5 hrs, then repeat the pattern. i take the 50mg since it takes 90min for the CR to kick in and the 50mg will take 45min to kick in, just about the time the 100mg starts to wear off. this isn't a whole lot better than your drug regime, my point here is it might be worth experimenting with CR. I also take .50-.75mg mirapex during the day, .375 at night +200CR, i think the small amount of mirapex makes my OFF time less severe. eating protein of course negates the l-dopa so i either eat and suffer the inevitable off or if i have the will power eat most of my protein in the evening.

i also use a TIMEX EXPEDITION WATCH which has a repeat count down timer which i set to beep every hr, a stop watch which i set everytime i take a dose so i know when i took the last dose, and 3 timers so i can set 3 doseage times. with those functions i can be sure an alarm goes off when i should take the next dose, whether i actually take it is another thing.