Intestinal expression and metabolic activity of the CYP3A subfamily in female rats

被引:31
作者
Aiba, T [1 ]
Yoshinaga, M [1 ]
Ishida, K [1 ]
Takehara, Y [1 ]
Hashimoto, Y [1 ]
机构
[1] Toyama Med & Pharmaceut Univ, Grad Sch Pharmaceut Sci, Sugitani, Toyama 9300194, Japan
关键词
CYP3A9; intestinal metabolism; rifabutin; testosterone;
D O I
10.1248/bpb.28.311
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The intestinal expression of the CYP3A subfamily was investigated in female rats, and the intestinal metabolism of two CYP3A substrates, testosterone and rifabutin, was examined and compared between males and females. CYP3A1/23 and CYP3A2 intestinal expression was barely detected in male and female rats. Although CYP3A9 was predominantly expressed in the female rat liver, its expression in the intestine was not different between the two sexes. The rate of testosterone 6beta-hydroxylation in the female intestine was similar to that for males. Rifabutin was also metabolized at similar rates in both intestines, although the metabolic rate was greater in the female liver. These results indicate that the intestinal drug metabolizing activity of the CYP3A subfamily is similar between males and females, and that CYP3A9 is involved in the intestinal metabolism of CYP3A substrates in both sexes.
引用
收藏
页码:311 / 315
页数:5
相关论文
共 27 条
[1]   Poor correlation between intestinal and hepatic metabolic rates of CYP3A4 substrates in rats [J].
Aiba, T ;
Takehara, Y ;
Okuno, M ;
Hashimoto, Y .
PHARMACEUTICAL RESEARCH, 2003, 20 (05) :745-748
[2]   Insights into gender bias: Rat cytochrome P450 3A9 [J].
Anakk, S ;
Ku, CY ;
Vore, M ;
Strobel, HW .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2003, 305 (02) :703-709
[3]   Distribution and induction of CYP3A1 and CYP3A2 in rat liver and extrahepatic tissues [J].
Debri, K ;
Boobis, AR ;
Edwards, RJ .
BIOCHEMICAL PHARMACOLOGY, 1995, 50 (12) :2047-2056
[4]   A novel cytochrome P450 3A isoenzyme in rat intestinal microsomes [J].
Gushchin, GV ;
Gushchin, MI ;
Gerber, N ;
Boyd, RT .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 255 (02) :394-398
[5]   Effect of experimental renal dysfunction on bioavailability of ajmaline in rats [J].
Hashimoto, Y ;
Aiba, T ;
Yasuhara, M ;
Hori, R .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 2001, 53 (06) :805-813
[6]   Effects of intestinal and hepatic metabolism on the bioavailability of tacrolimus in rats [J].
Hashimoto, Y ;
Sasa, H ;
Shimomura, M ;
Inui, K .
PHARMACEUTICAL RESEARCH, 1998, 15 (10) :1609-1613
[7]   Metabolism of rifabutin in human enterocyte and liver microsomes: Kinetic parameters, identification of enzyme systems, and drug interactions with macrolides and antifungal agents [J].
Iatsimirskaia, E ;
Tulebaev, S ;
Storozhuk, E ;
Utkin, I ;
Smith, D ;
Gerber, N ;
Koudriakova, T .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1997, 61 (05) :554-562
[8]  
Jäger W, 1999, DRUG METAB DISPOS, V27, P1505
[9]   NEONATAL TESTOSTERONE IMPRINTING OF HEPATIC-MICROSOMAL DRUG-METABOLISM AND A MALE-SPECIFIC FORM OF CYTOCHROME-P-450 IN THE RAT [J].
KAMATAKI, T ;
MAEDA, K ;
SHIMADA, M ;
NAGAI, T ;
KATO, R .
JOURNAL OF BIOCHEMISTRY, 1984, 96 (06) :1939-1942
[10]  
Koudriakova T, 1996, J PHARMACOL EXP THER, V279, P1300