Population Profile of Cytochrome P450 Isozymes in the Small Intestine of Japanese

Abstract

Cytochrome P450 (CYP) enzymes contribute to the first-pass metabolism of orally administered drugs in both the liver and human small intestine, thus influencing their bioavailability. Although the CYPs profile in the small intestine of Caucasians was reported previously, that of the Japanese population has not. We investigated CYP (1A2, 2C9, 2C19, 2D6, 3A4 and 3A5) mRNA levels and localization in the small intestine of Japanese. Localization of CYP protein secretion was observed by immunohistochemistry. CYP mRNA levels were analyzed using real-time reverse transcriptase polymerase chain reaction. In the small intestine of Japanese, CYP3A4 and CYP2C19 were the major and second most highly expressed components among these CYPs, present in 63.2% and 21.3% of our subjects, respectively. Our results showed differences between Japanese and Caucasians in the CYP profiles in the small intestine. Respective CYP isozymes in the Japanese small intestine indicate the possibility of influencing first-pass metabolism or drug interactions.