On Tue 06 May, I received the following email from William E. Evans. I started
 to write a short answer, but it turned out long. Nonetheless, I suspect that
 a few more people may find it useful, so with Bill's agreement, I am
 re-sending it to the list:

 Brian,

 I'm going to call my neurologist (a PD specialist) to ask about this, but I'd
 also like to have your opinion on this question.

 I'm taking one 25/100 Sinemet tablet three times a day.  When I told the
 neurologist that I didn't see major improvement he suggested 2 tablets three
 times per day. I thought that that was quite a lot for an early stage PD
 patient.  I have stayed on the 3 per day for the past 3 months.

 To determine whether the Sinemet was in fact helping, I stopped taking it for
 three days.  While the negative change was obvious, it was not disastrous.

 After all that, the question is:  Is there a finite amount of Sinemet that one
 can take before its effectiveness diminishes?  To rephrase the question, if I
 take six tablets per day versus three tablets per day, do I shorten the length
  of time that Sinemet will be effective (e.g., useful for four years versus
  five).

  Thanks for your postings.  They are always enlightening.

  Bill Evans
                   ==============================

 Hello Bill, I hope you find my comments useful.  First, we had better get a
 few terms defined. A very important concept is the effective duration of a
 Sinemet tablet. This is simply the time during which the output of Dopamine
 from the tablet (in the brain) equals or exceeds the minimum quantity of
 dopamine required by your brain. The effective duration depends on many
 things, which is why I will have to talk in generalities. Factors which can
 play a part are for instance:

 The rate of absorbtion of the tablet through the walls of the small
 intestine, which is affected by how food you have eaten, and how recently ;
 the speed of transport through the bloodstream to the brain; the time taken
 to cross the blood/brain barrier; and probably several other things that I
 have forgotten or don't know.
   The point is, that the effective duration is a very personal item, which
 will slowly change as your PD progresses. To save time, I will call it the
 ED for now.

 If you know your ED, which is one of the outputs of my notorious analysis
 program (Don't worry, you won't need it for a few years yet), then it is
 possible, by taking the next tablet just BEFORE the last tablet runs out of
 its ED, to make a sort of seamless join between two tablets so that the
 combined output of the old and new tablets remains more-or-less constant.

 Now, suppose you get up at 8:00 am and have an 18 hour day, and a 4 hour ED.
 By stringing the tablets together, to make as near to a straight line, you
 will have achieved the optimum output from your tablets, taking 1 at 8:00,
 1 at 12:00 1 at 16:00, 1 at 20:00, and finally 1 at 20:00  (the last tablet
 would overlap into sleeping, but possibly to good effect on sleep.

 If you take fewer tablets than the mumber indicated by the ED above, nothing
 much will happen, except that gaps will appear in your condition where the
 old tablet runs out before the new tablet has arrrived. However, if you try
 to add another Sinemet into the schedule, then at points where the tablets
 overlap the levodopa flow will rise up to double the single-tablet flow,
 which is a gross increment, and in all probability far more than you need.
 But there is no magic in the choice of 100 mg of levodopa in each Sinemet
 tablet. You could try say 1 and a quarter tablets where previously you took
 one, until you achieve the magic flow rate which gives 'normal conditions'.

 Of course, it may turn out that a continuous flow of 1 tablets-worth of
 levodopa is itself too high - it would be for me for instance - so what I do
 is take Madopar 62.5 dispersible tablets as my basic unit. They are better
 because theyonly have 50 mg of levodopa, and I can take 1 and a 1/2 every 2
 hours, and get precisely the right amount (2 hours is my ED by the way :that
 is because I have had PD for 18 years (Actually 24 years since first
 symptoms).


 Well ! that's quite a lot of words, and I haven't answered your question
 yet. You should know that you are asking about a subject which is far from
 settled even among neurologists. Consider this fact: If I were to take a
 Sinemet 50/200 (i.e. a large overdose). I would go into wild dyskinesias and
 would be in severe physical discomfort. Now suppose I gave the same tablet
 to a notmal healthy person: what would happen to him? the astonishing (to me
 at least) answer is - nothing at all.  The reason why is that a healthy
 person, as you probably know, has about 10 times the number of dopamine
 -producing cells, and when an input of 200 mg of tablet- produced dopamine
 happens, this huge number of excess cells just throttle back a bit and make
 room for the tablet.

 Now we are coming to the crunch bit. A newcomer like yourself still retains
 the ability to swallow and absorb quite large doses of levodopa. Thus, to
 come back to your case, If you do double-up your tablets as your neurologist
 has suggested, your system will essentially take as much as it needs, and
 absorb the remainder by throttling back the still-functioning cells of which
 you still have quite a few, and I have very little. The question is: is it
 better to throw large doses of levodopa at the brain, and leave your system
 to sort it out, or should you adopt the approach which I explained in the
 first part of this large email, and only give your system enough dopamine to
 make up for the missing quantity in our brain?

 No doubt you will have gathered that I prefer the latter approach, and yet I
 don't know of any factual evidence which proves that the block-buster
 approach causes any harm to the patient. My choice is based on instinct as
 much as anything. I have questioned quite a lot of neuros on this subject,
 and they appear to be split about 50/50, so they are not much help. Your
 neuro appears to be inclined to the blockbuster route, so I hope that I have
 at least been able to shine a light so that you can see both of the choices.

 By the way, my charts A and B are illustrations of the same subject. If you
 would like copies and are using Windows 3.1 or Windows95, let me know.

 One last thing, Bill: I have written such a lot of words, and this subject
 does interest a lot of PWPs, so I wonder if you would mind if I opened it up
 to the whole list? Please let me know yes or no

 Regards,
--
Brian Collins  <[log in to unmask]>