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We are planning to use omeprazole as a probe substrate to examine the
inhibition of CYP2C19 by one of our drugs in a clinical study.
Literature suggests that we could take a single sample at 2 h and
measure the ratio of Omeprazole to its 5-OH metabolite. My question is
- Is this valid for delayed release omeprazole (the only kind available
in the US currently) or an immediate release (which may have been
introduced earlier and used in the investigations in the literature)?
The FDA website
fuseaction=Search.Label_ApprovalHistory#apphist) does not mention
anything about the IR product but a colleague who worked for Astra
Zeneca says that the IR product was introduced originally.
Any help would be greatly appreciated.
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I don't think you need to have an IR product for PPIs to do the kind of
trial you are planning. The Tmax for PPIs are mostly around 1.5-2.5
after oral administration.
The reason for PPIs to be formulated to be "delayed" release is to
PPI drug substances to be destroyed by the stomach acidity. Once the
coated granules of PPIs enter the higher pH environment in the small
intestines, the drug substances are immediately released and
You may see that lansoprazole is the only PPI that has both approved
suspension and orally disintegrating tablets available, but both of
formulations are in nature for the ease of use for patients with
swallowing. Neither will enhance the rate of absorption.
If you really need IR formulation for your study, I suggest you read the
following article to prepare suspension with sodium bicarbonate:
Comparative pharmacokinetics and pharmacodynamics of lansoprazole oral
capsules and suspension in healthy subjects.
Am J Health Syst Pharm. 2001 Aug 15;58(16):1512-9.
Doan TT, Wang Q, Griffin JS, Lukasik NL, O'Dea RF, Pan WJ.
Omeprazole in its base form is immediate-release in nature. As mentionedBack to the Top
previously, it will be inactivated in gastric acid without an enteric
OR a buffer and will not be absorbed to exert its pharmacologic effect.
Commercially available preparations of omeprazole are all
A new commercial product containing 1680 mg of sodium bicarbonate and
of omeprazole base was recently approved by the FDA but is not yet
marketed. The Tmax for this product is at approximately 30 minutes.
For years, clinicians have been compounding a similar formulation as
described in the link provided by the previous poster.
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