# Linzess / Linaclotide half life



## twonK (Oct 30, 2006)

Hi,

all I can find about its half-life is variations of



> Concentrations of linaclotide and its active metabolite in plasma are below the limit of quantitation after oral doses of 145 mcg or 290 mcg were administered. Therefore, standard pharmacokinetic parameters such as area under the curve (AUC), maximum concentration (Cmax), and half-life (t½) cannot be calculated.


which isn't very useful. Anyone care to take a punt at the half-life?

I'm asking since 145mg / day causes loads of pain but does get my bowels moving. Therefore I'm planning to take it every other day (or even every x days).

Thanks in advance,

Pete


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## Kathleen M. (Nov 16, 1999)

Since it doesn't really leave the GI tract, you really can't have a how long does it take your body to reduce the concentration in the blood by 1/2 type of measurement.



> Nevertheless, the presence of parent and active metabolite in the feces demonstrates that some active peptide is available to stimulate the GC-C receptor throughout the small intestine and colon.


Looks like along the way from mouth to anus the drug is metabolized, but the metabolite is also active so however long it takes for it to get out of the system (whatever your transit time while taking the drug) is how long at least some is available to be acting on the intestines.

Is it the kind of thing where you could split the dose? So instead of some parts of the stool having all of it and then a section with nothing maybe taking a lower dose every day may be useful? Hard to know.


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## twonK (Oct 30, 2006)

I'm confused







Are you saying that it's active in the gut and blood?

Can't split the dose - it's in a capsule. FWIW I stopped taking it over two days ago and I still had a BM this a.m. (which would never happen normally) so clearly some agent somewhere in my body is still at work.


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## Kathleen M. (Nov 16, 1999)

No.

It does not get into the blood stream. It stays in the gut.

It is broken down into an active metabolite (which also effects the gut) and that metabolite stays in the gut.

So if you have a transit time of 3 days, it takes 3 days for the stuff to get out of your gut as it travels with the feces.

The reason they cannot measure half life is half life is all about how long it takes to get the drug (or active metabolite of the drug) out of your blood. If it was NEVER in the blood you can't measure how long it took to get pulled out of the blood by your kidneys or liver. The measure each and every time is 0, so no half life can be measured.


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## twonK (Oct 30, 2006)

got it. What threw me was



> Looks like along the way from mouth to anus the drug is metabolized


since I thought metabolized meant "enters the blood stream".

So really "half-life" doesn't come into it since 100% of it is in your body until you [email protected] it out (whereby it goes to ~ 0%), right? So I guess I'll find out what my transit time is on Linzess.

I find it weird that it took 2 weeks to start having an effect for me. Perhaps I was so backed up it took a long time to build up in my gut?


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## Kathleen M. (Nov 16, 1999)

Absorbed is entered the blood stream

Metabolized means something somewhere (anywhere) in the body added something to it, or tore something off of it.

There are two things that go on with medications, IMO, that can be why they aren't an instant cure. 1. If it sticks to something or accumulates in something (like the cells lining the intestines) it may take awhile to build up to the level needed.

2. What is the reaction of the cells and does that response take time to fully develop or does it turn on and off like a light switch. Like with an antidepressant the blood level generally comes up fairly fast and stabilizes, but some of the responses of the nerves take a few weeks to show up. (as nerves are slow to grow and change). So even if your get enough in after a day or three you may not see a response for a month or two.


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## twonK (Oct 30, 2006)

gotcha. Many thanks, another excellent explanation! I'm certainly familiar with how AD's can operate (or more often not operate).


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