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Bobib
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Quote Bobib Replybullet Topic: Extended release PPIs?
    Posted: 23 Feb 2017 at 4:17pm
As some of you already know, one of the problems with PPIs, especially for night refluxers, is the short half life of PPIs in the blood for most people (usually around 1 hour), combined with the partial activation of proton pumps at any one time, and the continued renewal of proton pumps (which happens to occur at a greater rate at night).

This means that even on high dose PPIs taken twice daily, acid suppression isn't always effective and often fails with night refluxers.

One of the ways to deal with this is slow release PPIs, or PPIs with a much longer half life. However, as far as I can see no such product is on the market in the UK despite many of these having been undergoing testing for over 10 years. One example of such a drug is tenatoprazole which has a half life of 7-8 hours and achieves much better nocturnal acid suppression than PPIs available in the UK. Tenatoprazole is prescribed in Japan.

Does anyone know what the approval process in the UK is like, and why this drug (and others like it) has not been made available here, and whether it is likely to be in the future?

Some interesting reading:

http://www.jnmjournal.org/journal/view.html?uid=32&vmd=Full

http://www.medscape.org/viewarticle/506526_2
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jcombs99
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Quote jcombs99 Replybullet Posted: 23 Feb 2017 at 4:52pm
           It called FUNDS Bob even if they ever get them approved the common person will never get them .I tried them like 5x more cost and they didn't work any better then my Precvid .I've never been into that half life stuff .The best I every did was 60mg per day 15mg @ 7am 30mg an hour before dinner and 15mg before bed . That's what u Call Timed Released !! Cheap but works hope ur Drug and Timing works 4 U .Hope I didn't scare anyone with this post .

CHEERs

CHEERs
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chrisrob
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Quote chrisrob Replybullet Posted: 23 Feb 2017 at 4:56pm
My own view about half life of this drug is that it's actually a bit of a red herring.

This paper The dose of omeprazole required to achieve adequate intraesophageal acid suppression in patients with gastroesophageal junction specialized intestinal metaplasia and Barrett's esophagus. published in Digestive Diseases and Science in 2013, concluded, The majority of patients with Barrett's esophagus were controlled with once daily low dose PPI and only a minority required twice daily dosing

The JNM link you posted concludes there are still many areas of unmet need in GERDs, so new therapies are needed. Current compounds under development include improved PPIs, TLESR reducers, esophageal-specific pain modulators, and mucosal protectants. I would have thought PPIs with a longer half life was a fairly low priority since most patients find their efficacy over 24 hr period is sufficient (particulalrly after a few days of initial build up).

The Medscape article, whilst providing an interesting presentation is sponsored by Santarus who manufacture and produce Zegerid in US. Zegerid is a combination drug of omeprazole with sodium bicarbonate to reduce possibility of being destroyed by stomach acid before it reaches the duodenum rather than being enteric coated.

PPIs are effective at reducing acid but not for reducing reflux. Nocturnal refluxers need to establish lifestyle modifications to enable reflux reduction rather than rely on more PPIs. If excess acid is also found at night, the addition of an H2 blocker at night is usually sufficient or on-demand Gaviscon.

There are very many other PPIs. Tenatoprazole is one. Others are Ilaprazole, Picoprazole, Timoprazole. Doubtless their manufacturers would suggest their drugs are better than those commonly prescribed, but when tests have shown them to be no better, why should the more expensive newer creations be prescribed?
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steveb8189
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Quote steveb8189 Replybullet Posted: 27 Feb 2017 at 9:35am
I was confused about half life for a while too but actually for the opposite reason. When my dose of Nexium was upped to 40mg / day I was certain there was an accumulative effect in my body. Over a number of weeks I would start to feel miserable and then with a couple of days off I would feel fine again for another couple of weeks. I did a bit of maths to see how much is left in your body after a 24 hour period and it's negligible - due to the way the half life works, even the negligible amount is then wiped out the next day and cannot accumulate.

That's when I came to the same "red herring" conclusion as Chris that the drug may have been metabolized but the effect. From wikipedia:

"The PPIs are given in an inactive form, which is neutrally charged (lipophilic) and readily crosses cell membranes into intracellular compartments (like the parietal cell canaliculus) with acidic environments. In an acid environment, the inactive drug is protonated and rearranges into its active form. As described above, the active form will covalently and irreversibly bind to the gastric proton pump, deactivating it."

To me, this means that once the PPI is "bound" to the proton pump and doing its business it will no longer be present in the blood stream. This means that it continues to be effective AFTER the half-life would prove it has been metabolised.

Personally, my primary symptom is nighttime reflux and I find 20mg of Nexium first thing in the morning fully resolves that - I may be lucky but it proves they have a longer lasting effect.

I still haven't worked out why I get the strange feelings after a couple of weeks - perhaps elevated gastrin levels - or maybe I just get down about taking pills
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