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Dear colleague,
I'm a Ph.D who's working with PB/PK models. I have question on the
determination of the hepatic extraction coefficient Eh. This
coefficient
is essential for the simulation. Normally, it is approximate by Eh =
Clint.Fu / Qh+Clint.Fu.
Clint is determined with Rats hepatocytes. The problem, I have a
better
prediction when I neglect the unbound fraction for compounds which
have protein binding < 95%.
Have You information about this ?
Sincerly,
Luttringer Olivier e-mail: olivier.luttringer.-a-.roche.com
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Scott Obach of Pfizer has studied the protein binding of three drugs in
microsomes and found that it depends on the drug. For example, propranolol
gave a good prediction of in vivo data when protein binding was disregarded
whereas warfarin gave a poor correlation. Please see,
Nonspecific binding to microsomes: Impact on scale-up of in vitro intrinsic
clearance to hepatic clearance as assessed through examination of warfarin,
imipramine and propranolol
R. Scott Obach, Drug Metabolism and Disposition, 25(12), 1997, 1359-1369.
Chandrani Gunaratna
Chandrani Gunaratna, Ph.D.
Senior Research Chemist
Bioanalytical Systems
2701 Kent Avenue
West Lafayette, IN 47906
Phone: (765)463-4527
E-Mail: prema.aaa.bioanalytical.com
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