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To all subscriber,
Could someone tell me the best analytic assay to use when processing CYP
3A4 drug-drug interactions (in vitro/ in vivo)? I need references to
articles or text books. I will appreciate each individual efforts and
Is it appropriate to use microsoft excel linear regression (R2) when
calculating kel for AUC? How do you calculate elimination rate constant
(kel) with microsoft excel using semi-log graph or which program do you
Thanks a lot!
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I have tried an assay by Gentest. It uses substrates for CYP3A4, or
other P450 enzymes, which become fluorescent after metabolism. Test
drugs can be added to see if there is inhibition of the enzyme. For
example, ketoconazole will stop much of the formation of fluorescent
product. The problems with this assay are that some of the drugs you
may be interested in could also have fluorescence and interfere with the
test. Also solvents for the drugs affect the CYP3A4 activity
differently depending on which solvent and how much is needed.
The Gentest webpage is found at:
For some drugs it might be easier to look directly at the formation of
metabolite with HPLC or LCMS in presence of CYP3A4 +/- the interacting
As for in-vivo examples of drug-drug interactions a topical example is
the interaction betweens the chemotherapy agent Irinotecan and the
anti-depressant remedy St. John's Wort. This appear to reduce levels
of the active metabolite of Irinotecan by inducing CYP3A4 activity.
Effects of St. John's Wort on irinotecan metabolism.
Mathijssen, R. H. J. et al.
J. Natl Cancer Inst. 94, 1247-1249 (2002)
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