About medication

As a member of the Science and Ethics group of the Dutch Parkinson association, I had to judge a study that was investigating the usability of a drug made from mucuna pruriens.
The seed powder of Mucuna pruriens has long been used in traditional Ayurvedic Indian medicine for Parkinson-like diseases. The seeds contain levodopa and seemed to work as good as modern medication where ldopa is combined with a decarboxylase inhibitor.

There has been a study (Katzenschlager R J Neurol Neurosurg Psychiatry. 2004 Dec;75(12):1672-7.), but this was not very usable to us because the study has only a very limited number of respondents. Further the main conclusion was negated by an obviously faulty figure that actually proofed that mucuna was the worst alternative while the text stated the opposite.

Still there is something about the mucuna project that I think we can learn from. It is what in recent publications is called the dirty drug concept. A drug composed of different active components may work better than the components separately administered.

In pharmacokinetics three important parameters are used to describe the characteristics of a drug:
- Cmac, which is the maximum plasma concetration
- Tmax or the time to reach Cmax
- Half-life, the time that is needed to reach half of Cmax.

The problem with PD is what they call the therapeutic window. If you take too much medicine you get side effects, if you don’t take enough the symptoms are not controlled adequately. This therapeutic window narrows during the development of the disease. It becomes a problem to keep levels of L-dopa within the therapeutic window.

A method that I use for myself, and that seems to work, is to use a diversity of drugs at the same time. I use levodopa together with benserazide and carbidopa. further I take a dopamine agonist (ropinerol) and I’m planning to use amantadine.

One reason why this concept works is that the medicines I use have different values for Tmax. So the top of the graph is reached at different moments in time. The tops aren’t high enough to cause side effects. An old report (Menek Goldstein a.o http://www.neurology.org/cgi/content/abstract/34/2/227) from the University New York wrote the following on combined us benserazide and carbidopa at Parkinson’s disease:
"The pharmacokinetics of levodopa differs when it is combined with benserazide or carbidopa. Peak dopa levels are higher, occur sooner, but decline more rapidly with benserazide. ..... Benserazide was combined with carbidopa in 38 patients who were experiencing a diminished response to carbidopa, .... Ten of the patients improved on the combination of benserazide and carbidopa, with a 30% decline in disability. .... The combination of carbidopa with benserazide is useful in some parkinsonian patients.

Further the time that is needed to metabolise the drug is considerably different in levodopa and dopamine agonists (Half-life). This spreads the effects of the medication in time.
Another method that in my opinion is equally important is to spread the use of medication evenly throughout the day. By taking less medicine, more often, plasma levels don’t get too high or too low.

I would appreciate some feed-back on this matter. Tell me what is wrong or right in my reasoning. In my opinion patients should actively try and fight this disease. And we have a definite advantage in the fact that we can feel what medication or therapy does to us. Something healthy researchers lack. If you have time please visit http://www.parkinsonhuis.nl/parkinso...estionaire.htm and fill in the questionnaire and become a member of our patients panel. Every six months your symptoms will be recorded. The aim is to find correlations both in symptoms and patients, and eventually to predict the development of the disease.