Has anyone tried to improve the effectiveness of their immediate release levodopa based drugs by taking the drug more frequently, while reducing the dose to maintain the total dose for the day at the original level?

For example, a total of 300mg of levodopa per day could be delivered by 3 doses of 100mg, 4 doses of 75mg, 10 doses of 30mg, 100 doses of 3mg, etc..

More frequent doses should even out the amount of levodopa in the body. But, as always, the devil is in the detail.

John

John, that is the challenge of carbidopa/levodopa. i'm sure your're aware that one way to do that is to dissolve your daily total dosage in water plus vitamin c, i think 500mg but probably not that critical and take it in liquid form. i haven't tried to do that even though i do have to take L/C every 3 hrs most of the time., maybe more often and that's all i take, both IR and CR, i still play around with he doseage everyday. lately i've been taking 125mg 1st thing in the morning (split a 25/250 IR) and take another 125 2hrs later, my theory is i need to replenish my depleted levodopa quickly and also the carbidopa, it also has a short half life. when calculating my total levodopa for the day, i modify 200mg CR to be bioequivalent to 120mg levodopa.

i can play around with my meds since i don't work, if i had a job and/or was a caregiver, i'd have to take my meds on a tight schedule. at that point, would likely take 125mg L/C upon wakening and then a 1.5 tabs of 50/200mg CR an hr later and develop some variation on that the rest of the day.

It seems to me that there is much that we can do to improve the effectiveness of existing drugs.

I have posted [1] on the effect on me of drinking Stalevo in ascorbic acid (vitamin C). This test showed a slightly faster response and a higher bio-availability than from taking the Stalvo normally. Clearly, one test of each form of delivery is insufficient to generalize from, but it certainly warrants further investigation.

Once you can drink the drug frequent dosing becomes practical: e.g. 100 sips during the day. At its simplest the equivalent of each pill could be put into a small bottle. To raise levodopa levels at the start of the day, one bottle could be drunk quickly, then the other bottles sipped during the day. A more advanced system could monitor the amount being drunk and recommend when to take more. This could be refined further by monitoring patient symptoms and adjusting the recommendations accordingly.

It is surprising that there is so little reporting of high frequency dosing. An exception is Palhagen who got PwP to drink their medications during the day [2]:
"After achieving an optimal dosing regimen, the nasointestinal tube was removed and the LCIG [levodopa/carbidopa intestinal gel] dosing schedule was converted to an oral treatment regime that PwPs could administer themselves by sipping or drinking the dissolved medication. This allowed for division of the daily-prescribed quantity into smaller, more frequent doses throughout the day."

A major disadvantage of the liquid medication method compared with the intestinal pump is that there is a delay in the delivery of the "drink" to the intestines. Are there other disadvantages?

Reference

[1] http://neurotalk.psychcentral.com/thread183360-2.html

[2] "The Dose-Finding Study nasoduodenal infusion of levodopa/carbidopa intestinal gel (LCIG, Duodopa®) as a dose-finding tool in parkinsonian patients with fluctuations"
Palhagen S.
European Parkinson's Disease Association
http://www.epda.eu.com/ru/parkinsons...finding-study/

John

i've read about frequent dosing using "liquid" sinemet in a number of general books on pd, one being "THE PARKINSON'S DISEASE TREATMENT BOOK" and a general procedure on calculating sinemet dosage. in all cases, they just recommend storing the mixture in a bottle with measurements marked on the side and pouring out the correct amount or having a cup with the correct volume marked on it. i imagine it is a hassle having to mix the stuff up daily and if you make a mistake can be problematic. not sure if you need to refrigerate it. seems L/C dissolves so readily and is easy enough to split you can take small amounts without having to dissolve it.

What would this have to offer over an extended release formulation? Isn't the effect the same, you're getting a constant feed of the drug instead of large amounts?


Or does the CR not keep the blood concentration high enough and mini bolus administrations are preferred?

Hammilton, quite rightly asks what frequent dosing has "to offer over an extended release formulation?"

Controlled release drugs have a role to play: they can get you near the right level of drug concentration and hold it there for several hours.

For patients with functioning dopaminergic neurons excess levodopa can be stored, converted into dopamine and released as required later. In this way the peaks and troughs can be levelled off to a large extent.

As the disease progresses dopaminergic neurons die off or cease to function correctly. The storage capacity is, therefore, lost. This leaves you following plasma levels of levodopa: too little and you are "off", too much and dyskinesia can occur.

At this stage, the longevity of the controlled release drug counts against it; it's been taken and will continue to deliver levodopa regardless of the present requirements.

Another problem is that most drugs come in a limited number of strengths. It will be rare for a person's requirements, based on body weight, diet, exercise etc., to be optimally met by one of the strengths available.

Let's make a rough estimate of the size of the discrete strength error. For instance, Stalevo comes in six strengths: 50, 75, 100, 125, 150, 200 mg levodopa. Suppose you relied only on one 100 mg pill taken four times per day, making no adjustments. And assume this really was the best strength for you to take. Roughly speaking this means that your real need lies between 87.5mg (half way between the strength you take and the strength below) and 112.5mg. So, the error goes from 0 to 12.5mg, giving an average error of approximately 6%.

High frequency dosing allows adjustments to be made to fit patients' requirements.

John