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The
panel on the left shows some of the major isoforms of CYP450 and the size of
the wedge reflects their relative roles in drug metabolism based upon the
number of drugs that are known to be metabolized by that particular isozyme. CYP3A is responsible for the metabolism of
the largest number of drugs followed by CYP2D6.
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The
panel on the right summarizes the relative quantity of specific P450 families
found in the liver.1 The
CYP3A family is present in the largest amounts. CYP2D6 accounts for less than 2% of the
total content of P450 in the liver, but, as shown on the left, is responsible
for the metabolism of a large fraction of drugs. A large amount of cytochrome P450 has not
yet been characterized.
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There is
tremendous variability between individuals in terms of expression of
cytochrome P450 isozymes. For example,
some people do not have active CYP2D6 at all, and it is very highly expressed
in others.
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Note: CYP2C on the graph on the right refers to
both CYP2C9 and CYP2C19.
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1.
Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. Interindividual
variations in human liver cytochrome P-450 enzymes involved in the oxidation
of drugs, carcinogens and toxic chemicals: studies with liver microsomes of
30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 1994 July;270(1):414-23.
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