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Hello,
Ketoconazole is considered a potent inhibitor of PGP but I can't
find any references discussing what concentrations are needed in vivo.
I've got one reference for in vitro that says the ketoconazole IC50
ratio
for PGP/3A4 is 60-150 which, if Ki is 0.5 microM for 3A4, means minimal
keto cons of 30 uM for half-maximal inhibition of PGP.
How clinically important is keto pgp inhibition relative the
interactions
it causes via 3A4?
If you had a NCE that was a PGP substrate, would keto be the agent you'd
choose to run a PGP interaction study with?
Thanks
Susan
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The following message was posted to: PharmPK
dear susan,
about the clinical relevance of pgp / 3A4 Inhibitors (such as
ketokonazole)
look up the literature of Benet and his group (such as Zhang / Benet,
clin
Pharmacokin. 2001:40 (3): 159-168, and others). If you intend to perform
studies, keep in mind the limited aqeous solubility of Ketokon
(somewhere
about 5µM)
all the best,
Philip
Philip Lienau
Schering AG
Research Pharmacokinetics
Tel.: +49 - 30 - 468 - 18507
Fax: +49 - 30 - 468 - 12238
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)