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Re: delivery difference

Posted by SFY on May 30, 2006, at 10:38:05

In reply to delivery difference, posted by Donna Louise on May 29, 2006, at 6:43:17

> It seems to me that I read somewhere that by transdermal delivery some of the unwanted type metabolites that result in first past gut metabolism in the liver are not created. Maybe one of the more amphetamine type metabolites?? I will see if I can find where I read that.
> At any rate, for me, I have had no side effects from the patch, maybe I wouldn't from oral administration either. I guess another plus with transdermal delivery is the slow and steady plasma state. no ups and downs. What do I know, just that I like it. May need to go to 9mg though for more depression relief.
>
> Donna

I posted this below in another thread that may have been overlooked:

EMSAM does deliver selegiline directly into the blood thereby significantly reducing its exposure to the GI tract. But because blood flows to all internal organs including the liver, intestines, and stomach there will be some selegiline exposure which explains why some people are having GI tract-related side effects.

According to one study:

Transdermal delivery of selegiline provides several pharmacological advantages over oral delivery. First, it sufficiently reduces exposure of the gastrointestinal tract to the drug to limit inhibition of intestinal MAOA activity. Thus, adequate gastrointestinal MAOA enzyme is left
intact to metabolize dietary tyramine. Second, transdermal administration of selegiline circumvents first-pass hepatic metabolism, which results in sustained high plasma levels of the parent compound with a concomitant decrease in metabolite formation. This provides sufficient brain concentrations of selegiline to produce an antidepressant effect, presumably involving substantial MAOA as well as MAOB inhibition. This also may permit the expression of additional pharmacological properties of selegiline other than MAO inhibition previously observed in vitro. At the same time, there is less exposure to L-methamphetamine and L-amphetamine metabolites than observed with oral selegiline.

http://ajp.psychiatryonline.org/cgi/content/full/159/11/1869

The EMSAM drug insert clearly states that at least 1 in 100 users may experience GI-related side effects such as "Constipation, flatulence, anorexia, gastroenteritis, vomiting."


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