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Hi, All:
Could anyone tell me in the Kitz-Wilson plot when we use it to
calculate KI and Kinact, the MBI inhibitor concentration we used here
is the final conc. in pre-incubation system or the final conc. in the
incubation system after 5~10 fold diluted?
[Google gave me:
http://wiz2.pharm.wayne.edu/biochem/enz.html
http://www.boomer.org/pkin/PK05/PK2005313.html
- db]
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The following message was posted to: PharmPK
It should be the final concentration in pre-incubation system because
that's
the concentration which inhibits the enzyme, you may find the following
papers useful too:
Grimm, S. W., H. J. Einolf, et al. (2009). "The conduct of in vitro
studies
to address time-dependent inhibition of drug-metabolizing enzymes: a
perspective of the pharmaceutical research and manufacturers of
America."
Drug Metab Dispos 37(7): 1355-70.
Ghanbari, F., K. Rowland-Yeo, et al. (2006). "A critical evaluation of
the
experimental design of studies of mechanism based enzyme inhibition,
with
implications for in vitro-in vivo extrapolation." Curr Drug Metab 7(3):
315-334.
Yang, J., M. Jamei, et al. (2005). "Kinetic values for mechanism-based
enzyme inhibition: Assessing the bias introduced by the conventional
experimental protocol." Eur J Pharm Sci 26(3-4): 334-340.
Regards
Masoud
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It should be the inhibitor concentration before dilution. One of the
main reasons for the dilution is avoid effect of direct inhibition.
Thanks,
Kishore
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The following message was posted to: PharmPK
The it is not the concentration at which inhibition is seen? That
seems a
bit off. What is the final concentration in the final mixture. That
is the
thing not the prediluted??? concentration.
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