title: Cytochrome P450 metabolic activities in the small intestine of cynomolgus macaques bred in Cambodia, China, and Indonesia.
abstract: Cynomolgus macaques, used in drug metabolism studies due to their evolutionary closeness to humans, are mainly bred in Asian countries, including Cambodia, China, and Indonesia. Cytochromes P450 (P450s) are important drug-metabolizing enzymes, present in the liver and small intestine, major drug metabolizing organs. Previously, our investigation did not find statistically significant differences in hepatic P450 metabolic activities measured in cynomolgus macaques bred in Cambodia (MacfaCAM) and China (MacfaCHN). In the present study, P450 metabolic activity was investigated in the small intestine of MacfaCAM and MacfaCHN, and cynomolgus macaques bred in Indonesia (MacfaIDN) using P450 substrates, including 7-ethoxyresorufin, coumarin, bupropion, paclitaxel, diclofenac, S-mephenytoin, bufuralol, chlorzoxazone, and testosterone. The results indicated that P450 metabolic activity of the small intestine was not statistically significantly different (<2.0-fold) in MacfaCAM, MacfaCHN, and MacfaIDN. In addition, statistically significant sex differences were not observed (<2.0-fold) in any P450 metabolic activity in MacfaCAM as supported by mRNA expression results. These results suggest that P450 metabolic activity of the small intestine does not significantly differ statistically among MacfaCAM, MacfaCHN, and MacfaIDN.
authors: Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd.
authors: Yasuharu
authors: Y
authors: Nakanishi
authors: Hiroyuki
authors: H
authors: Yamashita
authors: Tsuyoshi
authors: T
authors: Yoshikawa
authors: Takeshi
authors: T
authors: Tominaga
authors: Koichiro
authors: K
authors: Nojiri
authors: Yoshiharu
authors: Y
authors: Sunaga
authors: Atsunobu
authors: A
authors: Muneoka
authors: Kazuhide
authors: K
authors: Iwasaki
authors: Masahiro
authors: M
authors: Utoh
authors: Chika
authors: C
authors: Nakamura
authors: Hiroshi
authors: H
authors: Yamazaki
authors: Yasuhiro
authors: Y
authors: Uno
mesh_terms: D000818:Animals; D002160:Cambodia; D002681:China; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D007214:Indonesia; D007421:Intestine, Small / Q000201:enzymology*; D008252:Macaca fascicularis / Q000378:metabolism*; D008297:Male; D013045:Species Specificity
chemical_list: D003577:Cytochrome P-450 Enzyme System