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Hi,
I'm dealing with the compound which is a potential inhibitor of the CYP
3a4
(IC50 < 5 uM, in vitro rHu CYPs).
Since, intended rout of administration for the compound is nasal, I am
wondering if that implies a less risk for drug-drug interactions in
comparison to scenario in which the compound would be given orally.
Best regards
S.
Sinisa Stipanicic, MS Chem.
PLIVA Research Institute Ltd.
Drug Metabolism and Pharmacokinetics
Prilaz baruna Filipovica 25
10000 Zagreb, CROATIA
Phone: +385 1 372 2572
Fax: +385 1 372 1570
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A drug given orally has a higher chance to inhibit intestinal CYP3A and
cause drug-drug or even food-drug interaction.
The risk of your compound to cause drug-drug interactions will depend
on its absorption and how much will reach systemic circulation.
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Hi,
The potential for drug-drug interactions at the level of hepatic and GI
P450s is
certainly lessened by nasal administration. In addition the dose
administered is
probably less (?) by the nasal route than by an oral route so decreasing
inhibition potential as well.
P450s are quite active in the nasal system, especially in the 'smell'
process.
Local inhibition of nasal P450s may cause problems with the sense of
smell
Dave
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One of the important things to remember in this case is that what is
the intended dosage concentration? and what would be the maximal dose
absorbed or ingested as an oral dose after nasal administration?
Thixotropic formulations and other gel-based formulations may not have
the nasal to oral exposure profiles that some liquid formulations do.
This will become very important in the risk assessment of the potential
to cause effect.
Sanjeev Thohan, PhD
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)