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The following message was posted to: PharmPK
Dear all,
I would like to phenotype subjects for CYP2C19 and am not sure which
drug and/or which index is best to use. Many (old) publications are
availabe describing the use of the 8h-urinary ratio of
S-mephenytoin/R-mephenytoin following an oral dose of 100mg racemic
mephenytoin. Obviously there seem to exist some problems with the
stability of this ratio in urine (an acid labile metabolite of
S-mephenytoin seems to revert back to S-mephenytoin during storage
over more than 1-month) which causes trouble in extensive
metabolisers rather than poor metabolizers. Some use the the ratio of
4-OH-mephenytoin/dose of S-mephenytoin instead. Some propose
omeprazole PK saying this is better than mephenytoin indices.
Any help is welcome.
Kind Regards Conni
Dr. Cornelia Weber
Clinical Science Pharmacology
Hoffmann-La Roche Ltd.
(52/906)
Basel
phone +41 61 6888017
fax +41 61 6881043
E-mail cornelia.weber.aaa.roche.com
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The following message was posted to: PharmPK
Dear Cornelia,
For a reliable S/R mephenytoin index, you must perform the analysis before
and after strong acid treatment (1h in 12M HCl).
S/R ratio after hydrolysis is generally strongly increased in EMs, while it
remains unchanged in PMs.
see G. Tybring and L. Bertilsson, Pharmacogenetics 2:241-243, 1992.
rgds,
Armel Stockis
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)