On Thu 29 Jul, judith richards wrote:
>  29 July 1999
> Drug firms go all out to dazzle doctors
>
I have been trying to make sense of the apparently revolutionary result produced
by SmithKline Beacham by testing a combination of Levodopa and Requip. After all,
obtaining an increase in operating margin (between on the one hand Parkinson
tremor, and on the other hand levodopa-related dyskinesias) without compromise
is quite simply the Holy Grail which we are all chasing.

********************
To get to the bottom line in one leap- Those folk who are in the starting blocks
and quivering, just waiting for the Drug Store (Chemists) to open. can stand down:
The optimum margin available is the same as it was yesterday. SKB have just
wrapped the package in a different way.
*******************


The attached chart, which I have deliberately kept very basic, is essentially an
extract from my note "A Model to Describe the Effect of Levodopa on a Person with
Parkinson's Disease".  This paper can be read at Simon Coles web Site :

       http://james.parkinsons.org.uk/

I will attempt a rough diagram in this email, which may convey the  key message.


 |NN  Normal Behaviour
 |  NN
 |    NN
 |      NN
 |       NN
 |30       NN
 |           NN
 |             NN
 |               NN   A               B      C
 |                 NN
 |20                 NN-D+L_D+L_D+L_D+LD+L+C+DA+L+C+.................
 |                     NN            LLL
 |                       NN        LL   LL        DA
 |                         NN     LL      LL    DA
 |                           NN LL          LDA
 |10                          LLNN         DA LL
 |                          LL   NN      DA     LL
 |                        LL       NN  DA         LL
 |                      LL           NN
 |__________________ _LL_____________NN______________________________________
         30           40         50       60         70
                                                         ( AGE )

    NN  NN  NN     Normal Behaviour

    LL  LL  LL     Levodopa

   _D+L_D+L_D+L    Combination of Dopamine + Levodopa


 The diagram shows how I have worked my way through the levodopa tablets,
until I found the point where the Off-period shakes and the On-period
dyskinesias were almost super-imposed. (Point B) At this point,I then
introduced the dopamine agonist (Pergolide/Requip) and this takes me on to
point C where I am Balancing levodopa and Permax to obtain a stable point.
As this becomes a difficulty  I open up the Pergolide by 500 micro grammes
and so far, I have stayed ahead of the game. The advantage that I gain by
putting the pergolide in as slowly as possible is the minimum exposure to the
side-effects.

   If we consider what SKB did was doing, they picked a point about where I
was at age 50 , still on levodopa, but getting ready for change. Then they
started feeding their subjects the Requip in large quantities. This is an
acceptable way to go: the agonists, (All of the newer types from Permax on)
will perform as expected, although there is an increased risk of provoking
side-effects.
   The simplest way to describe what they have done is that they have
mortgaged the future, by using all the Requip up at a relatively early age,
they then have to cope  with advancing PD effects with only levodopa to manoeuvre.

This note is rather hurried, because I wanted to catch the debate which I can
feel, rumbling beneath my feet even as I write.

Comments please!!

--

Brian Collins  <[log in to unmask]>



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