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Dear All,
I will be working on drug interaction of an extract that has an
impressive antiinflammatory activity in vivo. I want to look at the
CYP450 enzyme isoforms it is likely to affect. Please, can someone
give me a pointer to the drugs that are substrates for the following
isozymes: 3A4, 1A2, and C19 in rats or mouse?
Thank you.
Titilayo Oyelola Fakeye
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The following message was posted to: PharmPK
Hi
We currently use Erod (ethoxyresorufine) for CYP1A, Prod
(pentoxyresorufine)for CYP2B, testosterone for CYP3A (for male rat)
Regards,
Francoise BREE
Xenoblis CRO
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Dear Fakeye
For CYP1A2, phenacetin or caffeine are selective probes. For CYP3A,
you could use testosterone, nifedipine, midazolam. About 2C19, rat or
mouse don't have 2C19. If you want 2E1 probe, I suggest 4-nitrophenol
In case it may help you please find out more information on some of
my papers.
1.Tassaneeyakul W et al. Validation of 4-nitrophenol as an in vitro
substrate probe for human liver CYP2E1 using cDNA expression and
microsomal kinetic techniques. Biochem Pharmacol. 1993 Dec 3;46(11):
1975-81.
2.Tassaneeyakul W et al. Specificity of substrate and inhibitor
probes for human cytochromes P450 1A1 and 1A2. J Pharmacol Exp Ther.
1993 Apr;265(1):401-7.
3. Tassaneeyakul W et al. Caffeine as a probe for human cytochromes
P450: validation using cDNA-expression, immunoinhibition and
microsomal kinetic and inhibitor techniques.
Pharmacogenetics. 1992 Aug;2(4):173-83.
4. Tassaneeyakul W et al.
Validation of 4-nitrophenol as an in vitro substrate probe for human
liver CYP2E1 using cDNA expression and microsomal kinetic techniques.
Biochem Pharmacol. 1993 Dec 3;46(11):1975-81.
Wichittra
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Here is a table that was extracted and modified from data reported by
IN vitro technologies in Baltimore, its a rather different look at
normalized values of the various substrates and metabolic activities
by percentage. I hope this helps. BD Gentest and IVT both have
similar tables. It'll give you an idea, not a direct answer.
Activity CYP Human SD Rat F344 WISTAR CD-1
CYP Content 100 115 152 115 304
COH CYP2A 100 0 0 0 0
CZX CYP2E 100 72 113 0 156
DEX CYP2D 1 100 1074 811 605 679
ECOD Multiple 100 85 129 33 700
MEPH CYP2C 100 20 11 7 478
PHEN CYP1A 100 62 192 61 1036
TEST CYP3A 100 61 28 4 175
TOLB CYP2C 100 82 110 31 314
Sanjeev Thohan, PhD
Director, DMPK
Exelixis, Inc
[Reformatted slightly, hopefully without error - db]
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The following message was posted to: PharmPK
Sanjeev,
Thanks for the wonderful table comparing CYP activities in humans and
rodents!
Can you please clarify if the results are for males, females, or both?
Best regards,
Jackie
--
Jacqueline Gibbons, Ph.D.
Pharmaceutical Consultant, Specializing in ADME-PK
148 Ricardo Avenue, Piedmont, California USA 94611
GibbonsJ.at.Pacbell.net
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