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Lately there have been reports of polymorphism in CYP3A4 activity. Can
someone advise me as to what constitutes a poor vs extensive
metabolizer?
Also, for midazolam clearance, does CYP3A4 play more important role
than CYP3A5?
Thanks,
Vernon
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Unlike some of the other P450s (such as 2D6, 2C9, 2C19 etc.), 3A4
polymorphism does not seem to have very strong functional significance.
Please check the reference below for detail:
Floyd MD et al. Genotype-phenotype associations for common CYP3A4 and
CYP3A5
variants in the basal and induced metabolism of midazolam in European-
and
African-American men and women. Pharmacokinetics. 2003
Oct;13(10):595-606.
With regard to MDZ clearance, work using recombinant P450s suggests
that the
Vmax/Km ratio of 1'OHMDZ formation for both CYP3A4 and CYP3A5 are very
similar, although this ratio for 4OHMDZ formation is a little higher for
CYP3A4 compare to CYP3A5. Considering that at lower MDZ concentrations,
1'OHMDZ is the predominant product, I would guess that they may be
more-or-less equally imp for MDZ clearance.
Thanks,
Kishore
Kishore K. Khan, Ph. D.
Senior Scientist/Project Director
CellzDirect
8609 Cross Park Drive
Austin, TX 78754
Tel: (512) 615 2332
Fax: (512) 834 7767
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)