Diapositive 1

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Hello to all of you A VERY SHORT
PRESENTATION before more...much more...
Nov. 27th
2007
No pretention to show here any
scientific presentation but still a
rigorous one, in the language
currently understood by the vastest majority
Sorry for professionals, but
theyll have to adapt to !!
Anne Frobert Lyon, France
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PULSATILITY defines the variation in
dopaminergic stimulation upon specific
receptors. This factor is far the most important
one as in normal conditions dopaminergic
stimulation is a continuous one (tonic
stimulation) Upon the continuous modality are
added very short
and high peaks of release (phasic stimulation),
triggered by a new situation that suddenly
appears and requires immediate adaptation this
means, of course it is part of
all  the response to stressors . The lack of
respect to these functional conditions enhance
the loss of their regulations which results in
the so-called levo-dopa induced complications,
motor and psychiatric features impairing life in
advanced stages of IPD.
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PULSATILITY is linked with pharmacology (type of
drug) and pharmacokinetics ( actionn of drugs
through time) DOSE OF DRUG is important too
as there is a minimum in stimulation, a threshold
to overtake to obtain the continuous stimulation
and the effects for relief of symptoms But over
this threshold, more stimulation means no more
effect but complication. SO REMEMBER, DOSE IS
IMPORTANT BUT VARIATION OF DOSE IS THE MOST
IMPORTANT FACTOR
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EVOLUTION OF BLOOD LEVEL OF A DRUG AFTER ORAL
INTAKE (pharmacokinetics)
CONCENTRATION
Half-life (t ½) This is the amount of time it
takes for the drug concentration in the blood to
decline by half. The half-life is among the most
important PK measurements for how often a drug
has to be dosed (once-a-day or twice-a-day, etc).

Cmax This is the highest concentration of drug
in the blood that
is measured
after a dose
Tmax Time when C max appears
TIME (hours)
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AVERAGE RESULTANT LEVEL THRESHOLD LEVEL
ARL
Threshold level above which motor symptoms
relief appears ARL and Threshold must be
equivalent so that full efficiency appears (This
means ON is obtained when red line is above blue
line)
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PULSATILITY INDEX IP H / ARL
92
ARL
Height of largest variation
h 74
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Pulsatility Index is a good one when lt 25-30
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CASE N1
1 MADOPAR 125 1 COMTAN 200 8-11am-2-5-8 pm
REQUIP 2X2 mg 8-12am-4-8 pm
high variation IP 60
combinated MADOPAR-COMTAN and REQUIP without
modification of schedule
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CASE N1
low variation IP 30
curve with combinated MADOPAR-COMTAN and REQUIP
(same total dose/day) but with USE of HALF DOSE
of MADOPAR (62.5 instead of 125) MORE INTAKES and
DIFFERENT DISTRIBUTION OF SCHEDULE
high variation IP 60
combinated MADOPAR-COMTAN and REQUIP without
modification of schedule
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CASE N1
curve with combinated MADOPAR-COMTAN and REQUIP
(same total dose/day) but with USE of HALF DOSE
of MADOPAR (62.5 instead of 125) MORE INTAKES and
DIFFERENT DISTRIBUTION OF SCHEDULE
8 intakes a day, ON 13 to 15 hours, OFF none
Dyskinesia none
5 intakes a day, ON 6 to 8 hours, OFF 2 to 4
h Dyskinesia 2 to 4 hours at least
combinated MADOPAR-COMTAN and REQUIP without
modification of schedule
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OPTIMIZATION and QUALITY OF LIFE Same total
dose of drugs Constraint 3 intakes ( 8 versus
5) ON from 5 to 9 hours (13/15h versus 6/8h
) DURATION GOOD QOL X
2 OFF 0 (versus 2/4h)
Dyskinesia 0 (versus 2/4h) HIGH LEVEL OF
QOL X 2
CASE N1
curve with combinated MADOPAR-COMTAN and REQUIP
(same total dose/day) but with USE of HALF DOSE
of MADOPAR (62.5 instead of 125) MORE INTAKES and
DIFFERENT DISTRIBUTION OF SCHEDULE
combinated MADOPAR-COMTAN and REQUIP without
modification of schedule
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Few examples..

A.F
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No change of ARL at 150 IP from 66 to 25
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No change of ARL at 60 IP from 150 to 58
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stabilisation of ARL at 130 IP from about 60
to 28
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• Report of young womans upon curve demonstrate
  that daily schedule of symptoms follows red curve
  positions
• akinesia when red curve underblue one-
• dyskinesia at highest and lowest part of red
  curve variation
• As demonstrated by curve and parameters, at same
  time,
• A too low average level (ALR 49) triggers her
  akinesia
• Too high variations (IP 149) of short duration
  trigger dyskinesia
• on their own at highest and lowest part of curve
• Indeed a bad situation and index for performance
  of treatment only at
  57 of ideal possibility

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NEXT TO COME..

A.F