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    #1

    Arbaclofen Placarbil

    Arbaclofen Placarbil, a Novel R-Baclofen Prodrug: Improved Absorption, Distribution, Metabolism, and Elimination Properties Compared with R-Baclofen

    Abstract:

    Baclofen is a racemic GABAB receptor agonist that has a number of significant pharmacokinetic limitations, including a narrow window of absorption in the upper small intestine and rapid clearance from the blood. Arbaclofen placarbil is a novel transported prodrug of the pharmacologically active R-isomer of baclofen designed to be absorbed throughout the intestine by both passive and active mechanisms via the monocarboxylate type 1 transporter. Arbaclofen placarbil is rapidly converted to R-baclofen in human and animal tissues in vitro. This conversion seems to be primarily catalyzed in human tissues by human carboxylesterase-2, a major carboxylesterase expressed at high levels in various tissues including human intestinal cells. Arbaclofen placarbil was efficiently absorbed and rapidly converted to R-baclofen after oral dosing in rats, dogs, and monkeys. Exposure to R-baclofen was proportional to arbaclofen placarbil dose, whereas exposure to intact prodrug was low. Arbaclofen placarbil demonstrated enhanced colonic absorption, i.e., 5-fold higher R-baclofen exposure in rats and 12-fold higher in monkeys compared with intracolonic administration of R-baclofen. Sustained release formulations of arbaclofen placarbil demonstrated sustained R-baclofen exposure in dogs with bioavailability up to 68%. In clinical use, arbaclofen placarbil may improve the treatment of patients with gastroesophageal reflux disease, spasticity, and numerous other conditions by prolonging exposure and decreasing the fluctuations in plasma levels of R-baclofen.
    Arbaclofen Placarbil, a Novel R-Baclofen Prodrug: Improved Absorption, Distribution, Metabolism, and Elimination Properties Compared with R-Baclofen JPET
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    #2
    Arbaclofen Placarbil

    Interesting. :thanks:
    :nutso: I take pride in my humility :nutso:
    :what?:
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    Graph of My Drinking From July '09 to January '10

    Consolidated Baclofen Information Thread




    Baclofen for Alcoholism and Other Addictions
    A Forum
    Trolls need not apply

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      #3
      Arbaclofen Placarbil

      Phase 3 trial of arbaclofen placarbil (AP) for the treatment of spasticity in multiple sclerosis (MS) - September 13, 2010

      XenoPort announced that it plans to move arbaclofen placarbil (AP), also known as XP19986, into Phase 3 development as a potential treatment of spasticity in multiple sclerosis (MS) patients. This trial will be a multi-center, randomized, double-blind, placebo-controlled study designed to assess the efficacy and safety of AP as a treatment for spasticity in MS patients. Patients who complete this study would have the option to enter a long-term study to evaluate the safety of AP in MS patients. Following successful outcomes from these studies, XenoPort would file an NDA with the FDA using the 505(b)(2) application process.

      AP is a patented new chemical entity that is a Transported Prodrug of R-baclofen designed to engage natural nutrient transport mechanisms found on intestinal cell membranes, thereby gaining efficient entrance into the bloodstream. AP is then rapidly converted by high-capacity enzymes to the parent compound and natural substances with favorable safety characteristics. R-baclofen is an agonist of the target known as gamma amino-butyric acid(B), or GABA(B), receptor.
      Phase 3 trial of arbaclofen placarbil (AP) for the treatment of spasticity in multiple sclerosis (MS) - MPR

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        #4
        Arbaclofen Placarbil

        That's good info, thanks!:rockon:

        Two things always stop me when I think about arbaclofen as a sub for bac, besides the fact that it's probably more expensive.

        1. Baclofen works. While arbaclofen might be as good, if not better, the titration schedules, expected side effects, and the like are virtual unknowns. The wealth of support and info from people here at MWO is invaluable. Put it in a sentence: if it ain't broke, don't fix it.

        2. Baclofen has a long history as a safe and widely tolerable drug. I like that. A lot. While arbaclofen might be the same, as it is basically focusing on the same receptors, it is a BIG unknown.

        Arbaclofen might be what we're all on in the near future, but for now, I'm sticking with what I know. I will ask my doc who is an addiction specialist if he can look into it for me and report back. I won't see him for a few weeks tho.

        I'll keep it on the google news rotation to see if anything comes up. glad you started this thread!!!:thanks:

        Comment

          #5
          Arbaclofen Placarbil

          Can someone paraphrase this for me in layman terms. Can't follow it. Please don't worry about getting it 100% accurate. Paraphrases never are. Please.
          Started Baclofen 3/9/10 Hit my switch at 250mg on 21/11/10 3.125mg/Kg

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            #6
            Arbaclofen Placarbil

            I've edited my response:

            Arbaclofen Placarbil is a baclofen prodrug. It is a chemical that turns into a specific kind of baclofen thoughout your body through your body's metabolism. Benefits are better bioavailabilty (regular baclofen can only be absorbed in a small part of the GI tract; several folks here on MWO have hinted at problems with gastic bypass surgury and baclofen), longer duration of action (baclofen's short half-life requires frequent daily dosing, a prodrug that metabolizes slower would produce baclofen over a longer duration (and with less fluctuation of of baclofen/blood level, and as I've alluded to elsewhere, a (possibly) more desirable form of baclofen (see my thread on enantiomers). -tk
            TerryK celebrates 6 years of sobriety and indifference to alcohol thanks to baclofen

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              #7
              Arbaclofen Placarbil

              Thanks terry
              Started Baclofen 3/9/10 Hit my switch at 250mg on 21/11/10 3.125mg/Kg

              Comment

                #8
                Arbaclofen Placarbil

                terryk;1003163 wrote: I've edited my response:

                Arbaclofen Placarbil is a baclofen prodrug. It is a chemical that turns into a specific kind of baclofen thoughout your body through your body's metabolism. Benefits are better bioavailabilty (regular baclofen can only be absorbed in a small part of the GI tract; several folks here on MWO have hinted at problems with gastic bypass surgury and baclofen), longer duration of action (baclofen's short half-life requires frequent daily dosing, a prodrug that metabolizes slower would produce baclofen over a longer duration (and with less fluctuation of of baclofen/blood level, and as I've alluded to elsewhere, a (possibly) more desirable form of baclofen (see my thread on enantiomers). -tk
                I can't find that thread.
                Your time is limited, so don't waste it living someone else's life... And most important, have the courage to follow your heart and intuition. They somehow already know what you truly want to become. Everything else is secondary.

                Steve Jobs, Stanford Commencement Adress, 2005

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                  #9
                  Arbaclofen Placarbil

                  beatle;1003463 wrote: I can't find that thread.
                  https://www.mywayout.org/community/f2...ncy-43742.html

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