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		LISTSERV Archives
		PARKINSN Home
		PARKINSN March 1997, Week 1

Subject:

Re: SINEMET HALF-LIFE

From:

"Charles T. Meyer" <[log in to unmask]>

Reply-To:

Parkinson's Information Exchange <[log in to unmask]>

Date:

Sun, 2 Mar 1997 21:29:04 -0500

Content-Type:

text/plain

Parts/Attachments:

text/plain (116 lines)

<HTML><BODY>
Brian Collins wrote:&nbsp;

<BLOCKQUOTE TYPE=CITE>On Sat 01 Mar, Dennis Greene wrote:
<BR><I>&gt; Brian,</I>
<BR><I>&gt;</I>
<BR><I>&gt; The quote is accurate but incomplete. It was originally&nbsp; proceeded</I>
<BR><I>&gt; by the words &quot; With regard to Sinemet CR ---&quot;.&nbsp;
In Ernie's earlier</I>
<BR><I>&gt; posting, he said:</I>
<BR><I>&gt;</I>
<BR><I>&gt; &gt;Seeking clarification on the &quot;half-life&quot;, I was told
that the &quot;exponential</I>
<BR><I>&gt; &gt;decay rate&quot; referred to the drug once it was in the blood
plasma.</I>
<BR><I>&gt;</I>
<BR><I>&gt; and later</I>
<BR><I>&gt;</I>
<BR><I>&gt; &gt;Sinemet CR will,however, deliver its designed dosage evenly</I>
<BR><I>&gt; &gt;per hour until exhausted.&nbsp; At this point, the half-life
decay rate</I>
<BR><I>&gt; &gt;will again come into play for the drug remaining in the blood.</I>
<BR><I>&gt;</I>
<BR><I>&gt; I seems to me that as each of CR's deliveries arrives in the blood</I>
<BR><I>&gt; plasma the half-life decay rate will apply to it.&nbsp; If this
is indeed the</I>
<BR><I>&gt; case (a phrase I used in my original posting) the slowing down
of</I>
<BR><I>&gt; the decay rate will result in each new delivery of levadopa being</I>
<BR><I>&gt; delivered on top of the exponentially decaying residue of the previous</I>
<BR><I>&gt; deliveries resulting in a (probably) small increase in the drug
levels</I>
<BR><I>&gt; over the life of a CR tablet.</I>
<BR><I>&gt;</I>
<BR><I>&gt; Dennis.</I>
<BR><I>&gt;</I>
<BR><I>&gt; ++++++++++++++++++++</I>
<BR><I>&gt; Dennis Greene 47/10</I>
<BR><I>&gt; [log in to unmask]</I>
<BR><I>&gt; ++++++++++++++++++++</I>
<BR><I>&gt;</I>
<BR><I>&gt;</I>
<BR><I>&gt; ----------</I>
<BR><I>&gt; &gt; &gt;&nbsp; &gt; Dennis whrote</I>
<BR><I>&gt; &gt; &gt;&nbsp; &gt;</I>
<BR><I>&gt; &gt; &gt;&nbsp; &gt; 1.&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; the exponential
decay rate is operative on all deliveries of</I>
<BR><I>&gt; the</I>
<BR><I>&gt; &gt; &gt; drug, once they are in the blood stream.</I>
<BR><I>&gt; &gt; &gt; 2.&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; this in turn will result
in a small, but significant increase</I>
<BR><I>&gt; in the</I>
<BR><I>&gt; &gt; &gt; drug levels over the delivery period of the tablet, culminating
in a</I>
<BR><I>&gt; peak at</I>
<BR><I>&gt; &gt; &gt; the end of the dose.</I>
<BR><I>&gt; &gt;</I>
<BR><I>&gt; &gt;</I>
<BR><I>&gt; &gt;</I>
<BR><I>&gt;</I>
<BR><I>&gt;</I>
<BR>I do hate having to play the heavy over this dyskinesia discussion, but
we
<BR>cannot allow mathematics to be bent to suit our requirements. I simply
do
<BR>not see how the exponential decay of any number of parts of a CR tablet
can
<BR>ever result in an upturn as the end of the dose is reached , or at any
time
<BR>in fact.
<BR>
<BR>&nbsp;Dennis - you make referene to &quot; the slowing down of the decay
rate&quot; - where
<BR>did that come from? It does not really change anything though: The only
way
<BR>that the concentration of levodopa in the blood plasma can rise is if the
<BR>rate of transmission from the lower intestine increases. Now that would
seem
<BR>quite possible to me - the drug manufacturers can surely only approximate
<BR>a constant flow rate with the CR tablet. How about turning those fretile
<BR>imaginations to that area?
<BR>
<BR>Regards
<BR>--
<BR>Brian Collins&nbsp; &lt;[log in to unmask]&gt;
</BLOCKQUOTE>
&nbsp;Brian,
<BR>
<BR>I certainly would not see a slowing of the decay rate with CR but there
would be a higher blood level at the end of the dose than with regular&nbsp;
Sinemet.&nbsp; Repeated dosing with either type would result in a higher
blood level at the end of a fixed length of time at the end of the day
than at the beginning.&nbsp;&nbsp;
<BR>
<BR>The problem is that there are so many factors that affect the action of
the drug including absorption from the gut (and possibly even inactivation
before it leaves the gut,&nbsp; breakdown in the peripheral circulation-
decarboxalases, Mono amine Oxidase,&nbsp; COMT,&nbsp; and then crossing
the blood-brain barrier in competition with amino acids, then the variable
of the same enzymes at the cellular level - not to mention pre synaptic
reuptake and receptor hypo or hypersensitivity.&nbsp; With all those factors
constantly in flux it is amazing that any 2 doses lead to any reproducible
results.
<BR>
<BR>Charlie
<BR>
<BR>--&nbsp;
<BR>**********************************************************&nbsp;
<BR>CHARLES T. MEYER, M.D.&nbsp;
<BR>MADISON, WISCONSIN&nbsp;
<BR>[log in to unmask]&nbsp;
<BR>**********************************************************&nbsp;
<BR>

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