On Wed 15 Sep, Ivan M Suzman wrote:
> On Sun, 12 Sep 1999 20:01:32 -0700 "J. R. Bruman" <[log in to unmask]>
> writes:
>
> "Because cabergoline seems to have much fewer nasty side effects than
> bromocriptine, and especially since its half-life of 65 hours permits
> Parkinson's sufferers to sleep all night through,"
> ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
> ^^^^^^^^^^^^^^^^^^^^
> Hi from Maine to J.R., Brian, and everyone-
>
> Can we please come to a consensus about the meaning of the term,
> "half-life" ? Knowing what a half-life is could be of IMMENSE help in
> planning our daily medicaiton routines!
>
> I understand it to mean the usual time that elapses from the point that a
>
> medication takes effect, until that at which half of the medication has
> been used up. Am I close?
>
> Is this purely based on chem-lab analysis, or also on REAL human
> beings whose responses to a drug are closely monitored?
>
> What are thought to be the half-lives of some of the more convential
> PD drugs, like sinemet, madopar, sinemet CR, and selegeline?
>
Hello Ivan, you have answered your own question quite effectively, so I
will just add some background information. The term half-life originates
from the nuclear physics field, and is used to describe a process where
the rate of decay is proportional to the concentration of the substance
being measured. It is used typically in cases of radio-active decay, where
you could wait for tens or hundreds of years to measure the time required
for a nuclear bomb site to become 'safe', but the half-life of the
radiation can be determined much more quickly and precisely. Note that the
half life has little to do with safety, and is of more useful in that it
describes the shape of a decay curve. These 'exponential curves' all have
similar characteristics, in that they start off with a rush, and then
start to taper off: It's a case of the slower you go, the slower you go
(if you see what I mean). Also you will see that if taken to its logical
extreme, an exponential dekay NEVER reaches its equilibrium point, so
you have to resort to half lives to make sense.
I have a handy reference book (see ref.) which quotes the half lives
of Bromocryptine ( 3 - 8 hrs) Pergolide (3 - 4 hrs) and Cabergoline (65
hours). I am far from being sure about these numbers being consistent
with each other. Is the shape of the curves typically exponential - we
don't know. I find 65 hrs hard to swallow, and even harder to swallow
when I look at my own experience:- When I make a change to my Pergolide
dosage, I KNOW that it will take between 1 and 2 WEEKS for the effect to
become fully established. The same rules applied to Cabergoline would
produce ridiculous answers, so I am forced to conclude that half life
definitions are misleading when applied to some PD medications. The half-
life definition deals with the start of the process, but what matters to
us is the long uncertain, process as the concentration of the drug in
the blood stream strolls slowly towards zero.
Sorry if I have confused you even more; I suggest that in practice, both
Pergolide and Cabergoline can be regarded as SLOW : By that, I mean that
( If I can just turn the problem on its head for a moment) drugs like
Pergolide and Cabergoline (and the other agonists ??) cannot generate
short-term effects like levodopa - their effect is purely to affect the
mean level, taken over a period of days. I think this is good news, not
bad.
There remains the little worry - if Pergolide (3 to 4 hours) takes 2 weeks
to stabilise, how long will Cabergoline (65 hrs) take?. I am sure that
there are a few users who could settle that one ....
Regards
Reference: Comparative Review of Dopamine Receptor Agonists in Parkinson's
Disease. Uitti and Ahlskog. Mayo Clinic. CNS Drugs 1996 May 5 368-388
--
Brian Collins <[log in to unmask]>
