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<HTML><BODY> Brian Collins wrote: <BLOCKQUOTE TYPE=CITE>On Sat 01 Mar, Dennis Greene wrote: <BR><I>> Brian,</I> <BR><I>></I> <BR><I>> The quote is accurate but incomplete. It was originally proceeded</I> <BR><I>> by the words " With regard to Sinemet CR ---". In Ernie's earlier</I> <BR><I>> posting, he said:</I> <BR><I>></I> <BR><I>> >Seeking clarification on the "half-life", I was told that the "exponential</I> <BR><I>> >decay rate" referred to the drug once it was in the blood plasma.</I> <BR><I>></I> <BR><I>> and later</I> <BR><I>></I> <BR><I>> >Sinemet CR will,however, deliver its designed dosage evenly</I> <BR><I>> >per hour until exhausted. At this point, the half-life decay rate</I> <BR><I>> >will again come into play for the drug remaining in the blood.</I> <BR><I>></I> <BR><I>> I seems to me that as each of CR's deliveries arrives in the blood</I> <BR><I>> plasma the half-life decay rate will apply to it. If this is indeed the</I> <BR><I>> case (a phrase I used in my original posting) the slowing down of</I> <BR><I>> the decay rate will result in each new delivery of levadopa being</I> <BR><I>> delivered on top of the exponentially decaying residue of the previous</I> <BR><I>> deliveries resulting in a (probably) small increase in the drug levels</I> <BR><I>> over the life of a CR tablet.</I> <BR><I>></I> <BR><I>> Dennis.</I> <BR><I>></I> <BR><I>> ++++++++++++++++++++</I> <BR><I>> Dennis Greene 47/10</I> <BR><I>> [log in to unmask]</I> <BR><I>> ++++++++++++++++++++</I> <BR><I>></I> <BR><I>></I> <BR><I>> ----------</I> <BR><I>> > > > Dennis whrote</I> <BR><I>> > > ></I> <BR><I>> > > > 1. the exponential decay rate is operative on all deliveries of</I> <BR><I>> the</I> <BR><I>> > > drug, once they are in the blood stream.</I> <BR><I>> > > 2. this in turn will result in a small, but significant increase</I> <BR><I>> in the</I> <BR><I>> > > drug levels over the delivery period of the tablet, culminating in a</I> <BR><I>> peak at</I> <BR><I>> > > the end of the dose.</I> <BR><I>> ></I> <BR><I>> ></I> <BR><I>> ></I> <BR><I>></I> <BR><I>></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> Dennis - you make referene to " the slowing down of the decay rate" - 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 <[log in to unmask]> </BLOCKQUOTE> 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 Sinemet. 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. <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, breakdown in the peripheral circulation- decarboxalases, Mono amine Oxidase, COMT, 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. With all those factors constantly in flux it is amazing that any 2 doses lead to any reproducible results. <BR> <BR>Charlie <BR> <BR>-- <BR>********************************************************** <BR>CHARLES T. MEYER, M.D. <BR>MADISON, WISCONSIN <BR>[log in to unmask] <BR>********************************************************** <BR> </BODY> </HTML>