Takahiro Nakamura, Keizo Okada#,
Kiyoshi Nagata* and Yasushi Yamazoe
Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical
Sciences, Tohoku University,
Aramaki, Aoba-ku, Sendai 980-8578, Japan
#ﾊCurrent address: Tokushima Research Institute,
Otsuka Pharmaceutical Co., Ltd., Tokushima 771-0192, Japan
*ﾊTo whom correspondence and reprint requests should be addressed.
Abstract: Properties of cytochromeﾊP450 (P450) in rabbit intestines
have been investigated to assess the possibility of an experimental model
for human intestinal oxidation of drugs. Significant amounts of P450 and
cytochromeﾊb5 and activities of NADPH-cytochromeﾊP450 reductase
were detected in microsomes from rabbit duodenal, jejunal, ileac and colon
mucosa. All the small intestinal fractions mediated phenytoin, dextromethorphan
and testosterone oxidations. Several P450 forms belonging to the CYP1A,
CYP2C, CYP2D and CYP3A, but not CYP2B and CYP2E, subfamilies were detected
in these tissues by Western blotting. A good correlation was observed between
immunodetectable levels of CYP3A and activities of testosterone 6b-hydroxylation.
Small intestine, but not colon, CYP3A levels were increased by the pretreatment
of rabbits with rifampicin (50ﾊmg/kg for 4ﾊdays, p.o.). The extent of the
increase was similar between duodena and livers.
Keywords: CytochromeﾊP450, Intestinal mucosa, Rifampicin, Induction,
Testosterone 6b-hydroxylation
Copyrightｩ The Japanese Pharmacological Society 2000
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