PharmPK Discussion - Enzyme drug interaction assay

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On 7 Oct 2002 at 05:18:23, ck34.aaa.juno.com sent the message


Dear Fellows,

Could someone please tell me the best assay to use for CYP3A4 enzymes
drug interactions to do a standard curve / in vitro/in vivo analysis
with
references.

Is it appropriate to use linear regression (r2) to calculate AUC to get
the best fix straight line on Microsoft Excel with out a semi-linear
graph? What is the best program to use to calculate AUC, and be able to
extrapolate the lines on a semi-linear graph paper? I used Microsoft
excel but there is no semi-linear graph paper.  Please references to
text
or articles for both answers to my questions will be highly appreciated.
Thanks a lot!

Ollie Anum

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On 7 Oct 2002 at 14:27:28, NTeuscher.at.npsp.com sent the message


Gentest (www.gentest.com) has a fluorescent assay for 3A4 that is very
good for in vitro determination of drug interactions.

Nathan S. Teuscher, PhD.
Drug Metabolism Scientist
NPS Pharmaceuticals
420 Chipeta Way
Salt Lake City, UT 84108
Email: nteuscher.at.npsp.com

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On 7 Oct 2002 at 16:55:34, eoconnor.aaa.Therimmune.com sent the message


Look at the data.  Are they linear? Try several fits perhaps with
weighting
or go to the literature and use the curve fit published articles use.
ENzyme
kinetic, binding assays etc are linera over only a limited range
becoming
non linear at the upper or lower end or both. 4 parameter curve fits
work
well in the latter case but you must establish fit.
In excel, If you go into graph then  scattergram, select scale then
select
axis, you can select log scal for y and linear for x etc.

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