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Dear All
What is known about ethnic differences in PK and metabolism?
Would clinical trials conducted in Japan, India, UK and US be expected
to give significantly different results? If so, would territory -
specific dosing regimes be recommended for the (eventually) marketed
product? Alternatively, would different formulations be expected by
the Regulators in the different regions?
Regards
Ian Smith
[Is this not a big part of the 'new' field of pharmacogenomics? There
is discussion of this topic in a number of pk textbook. See
http://www.boomer.org/pkin/book.html for books by Humma, L.M. et al.;
Licinio, J. and Wong, M.L.; Shargel, L. et al. and other recent
textbooks. I have made a very simple start at
http://www.boomer.org/c/p4/c17/c1702.html - towards the end of the page
- db]
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The following message was posted to: PharmPK
Ian:
This is a big area of research right now. Ethnic differences in the
prevalence of poor metabolizers are known for many drugs. This can
certainly
have an impact on dosing regimens. You may have heard the news that
Rosuvastatin's Product Label this month because a population
pharmacokinetic
analysis revealed a 2-fold increase in median exposure in Asians (the
mechanism is yet apparently unknown). It is now recommended that Asians
start at half the dose of other ethnic groups. I do not know if the
Japanese
Product Label has been changed.
Carol Collins MD
[Interesting, I was just reading the AAPS weekly report with an entry
for this change. The prescribing information (from
http://www.crestor.com/c/crestor/ link towards the bottom) mentions
only 10% metabolism by P450 2C9 BUT 79% excretion by the hepatic route
(unchanged in bile ?). Also mention of 2 fold increased exposure to
Asian patients and dosage change Rev 03/05 insert - db]
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Dear Forum,
As a small aside to the present discussion, would this affect the
bioequivalence studies done for generic drugs? Afterall, both the
innovator and the generic drug is studied in the same population. How
much is the acceptability of bioequivalence studies done in other
countries to the USFDA?
Nisha. K R.
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The following message was posted to: PharmPK
Carol,
Rosuvastatin has been just approved in Japan this January.
Its package insert is not available online yet.
But the approved formulations are 2.5 mg, 5 mg and 10 mg
tablets suggesting lower dosage in Japan than the usual
10 mg once daily dose in the US.
Masaki Hiraoka
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