共 34 条
Identification of enzymes responsible for rifalazil metabolism in human liver microsomes
被引:15
作者:

Mae, T
论文数: 0 引用数: 0
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机构: Kaneka Corp, Takasago Res Labs, Takasago, Hyogo 6768688, Japan

Inaba, T
论文数: 0 引用数: 0
h-index: 0
机构: Kaneka Corp, Takasago Res Labs, Takasago, Hyogo 6768688, Japan

Konishi, E
论文数: 0 引用数: 0
h-index: 0
机构: Kaneka Corp, Takasago Res Labs, Takasago, Hyogo 6768688, Japan

Hosoe, K
论文数: 0 引用数: 0
h-index: 0
机构: Kaneka Corp, Takasago Res Labs, Takasago, Hyogo 6768688, Japan

Hidaka, T
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h-index: 0
机构: Kaneka Corp, Takasago Res Labs, Takasago, Hyogo 6768688, Japan
机构:
[1] Kaneka Corp, Takasago Res Labs, Takasago, Hyogo 6768688, Japan
[2] Univ Toronto, Fac Med, Dept Pharmacol, Toronto, ON M5S 1A8, Canada
来源:
关键词:
D O I:
10.1080/004982500406408
中图分类号:
R9 [药学];
学科分类号:
1007 ;
摘要:
1. The major metabolites of rifalazil in human are 25-deacetyl-rifalazil and 32-hydroxy-rifalazil. Biotransformation to these metabolites in pooled human liver microsomes, cytosol and supernatant 9000g (S9) fractions was studied, and the enzymes responsible for rifalazil metabolism were identified using inhibitors of esterases and cytochromes P450 (CYP). 2. The 25-deacetylation and 32-hydroxylation of rifalazil occurred in incubations with microsomes or S9 but not with cytosol, indicating that both the enzymes responsible for rifalazil metabolism were microsomal. K-m and V-max of the rifalazil-25-deacetylation in microsomes were 6.5 mu M and 11.9 pmol/min/mg with NADPH, and 2.6 mu M and 6.0 pmol/ min/mg without NADPH, indicating that, although rifalazil-25-deacetylation did not require NADPH, NADPH activated it. Rifalazil-32-hydroxylation was NADPH dependent, and its K-m and V-max were 3.3 mu M and 11.0 pmol/min/mg respectively. 3. Rifalazil-25-deacetylation in microsomes was completely inhibited by diisopropyl fluorophosphate, diethyl p-nitrophenyl phosphate and eserine, but not by p-chloromercuribenzoate or 5,5'-dithio-bis(2-nitrobenzoic acid), indicating that the enzyme responsible for the rifalazil-25-deacetylation is a B-esterase. 4. Rifalazil-32-hydroxylation in microsomes was completely inhibited by CYP3A4-specific inhibitors (fluconazole, ketoconazole, miconazole, troleandomycin) and drugs metabolized by CYP3A4 such as cyclosporin A and clarithromycin, indicating that the enzyme responsible for the rifalazil-32-hydroxylation is CYP3A4.
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页码:565 / 574
页数:10
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共 34 条
[1]
SERUM ESTERASES .1. 2 TYPES OF ESTERASE (A AND B) HYDROLYSING PARA-NITROPHENYL ACETATE, PROPIONATE AND BUTYRATE, AND A METHOD FOR THEIR DETERMINATION
[J].
ALDRIDGE, WN
.
BIOCHEMICAL JOURNAL,
1953, 53 (01)
:110-117

ALDRIDGE, WN
论文数: 0 引用数: 0
h-index: 0
[2]
ABSORPTION, DISPOSITION AND PRELIMINARY METABOLIC PATHWAY OF C-14 RIFABUTIN IN ANIMALS AND MAN
[J].
BATTAGLIA, R
;
PIANEZZOLA, E
;
SALGAROLLO, G
;
ZINI, G
;
BENEDETTI, MS
.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY,
1990, 26 (06)
:813-822

BATTAGLIA, R
论文数: 0 引用数: 0
h-index: 0
机构:
FARMITALIA CARLO ERBA SPA,ERBAMONT GRP,RES & DEV PHARMACOKINET & METAB,VIA C IMBONATI 24,I-20159 MILAN,ITALY FARMITALIA CARLO ERBA SPA,ERBAMONT GRP,RES & DEV PHARMACOKINET & METAB,VIA C IMBONATI 24,I-20159 MILAN,ITALY

PIANEZZOLA, E
论文数: 0 引用数: 0
h-index: 0
机构:
FARMITALIA CARLO ERBA SPA,ERBAMONT GRP,RES & DEV PHARMACOKINET & METAB,VIA C IMBONATI 24,I-20159 MILAN,ITALY FARMITALIA CARLO ERBA SPA,ERBAMONT GRP,RES & DEV PHARMACOKINET & METAB,VIA C IMBONATI 24,I-20159 MILAN,ITALY

SALGAROLLO, G
论文数: 0 引用数: 0
h-index: 0
机构:
FARMITALIA CARLO ERBA SPA,ERBAMONT GRP,RES & DEV PHARMACOKINET & METAB,VIA C IMBONATI 24,I-20159 MILAN,ITALY FARMITALIA CARLO ERBA SPA,ERBAMONT GRP,RES & DEV PHARMACOKINET & METAB,VIA C IMBONATI 24,I-20159 MILAN,ITALY

ZINI, G
论文数: 0 引用数: 0
h-index: 0
机构:
FARMITALIA CARLO ERBA SPA,ERBAMONT GRP,RES & DEV PHARMACOKINET & METAB,VIA C IMBONATI 24,I-20159 MILAN,ITALY FARMITALIA CARLO ERBA SPA,ERBAMONT GRP,RES & DEV PHARMACOKINET & METAB,VIA C IMBONATI 24,I-20159 MILAN,ITALY

BENEDETTI, MS
论文数: 0 引用数: 0
h-index: 0
机构:
FARMITALIA CARLO ERBA SPA,ERBAMONT GRP,RES & DEV PHARMACOKINET & METAB,VIA C IMBONATI 24,I-20159 MILAN,ITALY FARMITALIA CARLO ERBA SPA,ERBAMONT GRP,RES & DEV PHARMACOKINET & METAB,VIA C IMBONATI 24,I-20159 MILAN,ITALY
[3]
ACTIVITY OF KRM-1648 ALONE OR IN COMBINATION WITH ETHAMBUTOL OR CLARITHROMYCIN AGAINST MYCOBACTERIUM-AVIUM IN BEIGE MOUSE MODEL OF DISSEMINATED INFECTION
[J].
BERMUDEZ, LE
;
KOLONOSKI, P
;
YOUNG, LS
;
INDERLIED, CB
.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,
1994, 38 (08)
:1844-1848

BERMUDEZ, LE
论文数: 0 引用数: 0
h-index: 0
机构:
UNIV SO CALIF,CHILDRENS HOSP LOS ANGELES,DEPT PATHOL & LAB MED,LOS ANGELES,CA 90027 UNIV SO CALIF,CHILDRENS HOSP LOS ANGELES,DEPT PATHOL & LAB MED,LOS ANGELES,CA 90027

KOLONOSKI, P
论文数: 0 引用数: 0
h-index: 0
机构:
UNIV SO CALIF,CHILDRENS HOSP LOS ANGELES,DEPT PATHOL & LAB MED,LOS ANGELES,CA 90027 UNIV SO CALIF,CHILDRENS HOSP LOS ANGELES,DEPT PATHOL & LAB MED,LOS ANGELES,CA 90027

YOUNG, LS
论文数: 0 引用数: 0
h-index: 0
机构:
UNIV SO CALIF,CHILDRENS HOSP LOS ANGELES,DEPT PATHOL & LAB MED,LOS ANGELES,CA 90027 UNIV SO CALIF,CHILDRENS HOSP LOS ANGELES,DEPT PATHOL & LAB MED,LOS ANGELES,CA 90027

INDERLIED, CB
论文数: 0 引用数: 0
h-index: 0
机构:
UNIV SO CALIF,CHILDRENS HOSP LOS ANGELES,DEPT PATHOL & LAB MED,LOS ANGELES,CA 90027 UNIV SO CALIF,CHILDRENS HOSP LOS ANGELES,DEPT PATHOL & LAB MED,LOS ANGELES,CA 90027
[4]
URINARY METABOLITES OF RIFABUTIN, A NEW ANTIMYCOBACTERIAL AGENT, IN HUMAN VOLUNTEERS
[J].
COCCHIARA, G
;
BENEDETTI, MS
;
VICARIO, GP
;
BALLABIO, M
;
GIOIA, B
;
VIOGLIO, S
;
VIGEVANI, A
.
XENOBIOTICA,
1989, 19 (07)
:769-780

COCCHIARA, G
论文数: 0 引用数: 0
h-index: 0
机构: FARMITALIA CARLO ERBA RES & DEV ERBAMONT GRP,DEPT ANALYT CHEM,I-20014 NERVIANO,ITALY

BENEDETTI, MS
论文数: 0 引用数: 0
h-index: 0
机构: FARMITALIA CARLO ERBA RES & DEV ERBAMONT GRP,DEPT ANALYT CHEM,I-20014 NERVIANO,ITALY

VICARIO, GP
论文数: 0 引用数: 0
h-index: 0
机构: FARMITALIA CARLO ERBA RES & DEV ERBAMONT GRP,DEPT ANALYT CHEM,I-20014 NERVIANO,ITALY

BALLABIO, M
论文数: 0 引用数: 0
h-index: 0
机构: FARMITALIA CARLO ERBA RES & DEV ERBAMONT GRP,DEPT ANALYT CHEM,I-20014 NERVIANO,ITALY

GIOIA, B
论文数: 0 引用数: 0
h-index: 0
机构: FARMITALIA CARLO ERBA RES & DEV ERBAMONT GRP,DEPT ANALYT CHEM,I-20014 NERVIANO,ITALY

VIOGLIO, S
论文数: 0 引用数: 0
h-index: 0
机构: FARMITALIA CARLO ERBA RES & DEV ERBAMONT GRP,DEPT ANALYT CHEM,I-20014 NERVIANO,ITALY

VIGEVANI, A
论文数: 0 引用数: 0
h-index: 0
机构: FARMITALIA CARLO ERBA RES & DEV ERBAMONT GRP,DEPT ANALYT CHEM,I-20014 NERVIANO,ITALY
[5]
IN-VITRO AND IN-VIVO ANTIBACTERIAL ACTIVITIES OF KRM-1648 AND KRM-1657, NEW RIFAMYCIN DERIVATIVES
[J].
FUJII, K
;
TSUJI, A
;
MIYAZAKI, S
;
YAMAGUCHI, K
;
GOTO, S
.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,
1994, 38 (05)
:1118-1122

FUJII, K
论文数: 0 引用数: 0
h-index: 0
机构:
TOHO UNIV,SCH MED,DEPT MICROBIOL,OTA KU,TOKYO 143,JAPAN TOHO UNIV,SCH MED,DEPT MICROBIOL,OTA KU,TOKYO 143,JAPAN

TSUJI, A
论文数: 0 引用数: 0
h-index: 0
机构:
TOHO UNIV,SCH MED,DEPT MICROBIOL,OTA KU,TOKYO 143,JAPAN TOHO UNIV,SCH MED,DEPT MICROBIOL,OTA KU,TOKYO 143,JAPAN

MIYAZAKI, S
论文数: 0 引用数: 0
h-index: 0
机构:
TOHO UNIV,SCH MED,DEPT MICROBIOL,OTA KU,TOKYO 143,JAPAN TOHO UNIV,SCH MED,DEPT MICROBIOL,OTA KU,TOKYO 143,JAPAN

YAMAGUCHI, K
论文数: 0 引用数: 0
h-index: 0
机构:
TOHO UNIV,SCH MED,DEPT MICROBIOL,OTA KU,TOKYO 143,JAPAN TOHO UNIV,SCH MED,DEPT MICROBIOL,OTA KU,TOKYO 143,JAPAN

GOTO, S
论文数: 0 引用数: 0
h-index: 0
机构:
TOHO UNIV,SCH MED,DEPT MICROBIOL,OTA KU,TOKYO 143,JAPAN TOHO UNIV,SCH MED,DEPT MICROBIOL,OTA KU,TOKYO 143,JAPAN
[6]
IN-VITRO AND IN-VIVO ACTIVITIES OF THE BENZOXAZINORIFAMYCIN KRM-1648 AGAINST MYCOBACTERIUM-TUBERCULOSIS
[J].
HIRATA, T
;
SAITO, H
;
TOMIOKA, H
;
SATO, K
;
JIDOI, J
;
HOSOE, K
;
HIDAKA, T
.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,
1995, 39 (10)
:2295-2303

HIRATA, T
论文数: 0 引用数: 0
h-index: 0
机构: SHIMANE MED UNIV, DEPT MICROBIOL & IMMUNOL, IZUMO, SHIMANE 693, JAPAN

SAITO, H
论文数: 0 引用数: 0
h-index: 0
机构: SHIMANE MED UNIV, DEPT MICROBIOL & IMMUNOL, IZUMO, SHIMANE 693, JAPAN

TOMIOKA, H
论文数: 0 引用数: 0
h-index: 0
机构: SHIMANE MED UNIV, DEPT MICROBIOL & IMMUNOL, IZUMO, SHIMANE 693, JAPAN

SATO, K
论文数: 0 引用数: 0
h-index: 0
机构: SHIMANE MED UNIV, DEPT MICROBIOL & IMMUNOL, IZUMO, SHIMANE 693, JAPAN

JIDOI, J
论文数: 0 引用数: 0
h-index: 0
机构: SHIMANE MED UNIV, DEPT MICROBIOL & IMMUNOL, IZUMO, SHIMANE 693, JAPAN

HOSOE, K
论文数: 0 引用数: 0
h-index: 0
机构: SHIMANE MED UNIV, DEPT MICROBIOL & IMMUNOL, IZUMO, SHIMANE 693, JAPAN

HIDAKA, T
论文数: 0 引用数: 0
h-index: 0
机构: SHIMANE MED UNIV, DEPT MICROBIOL & IMMUNOL, IZUMO, SHIMANE 693, JAPAN
[7]
Pharmacokinetics of KRM-1648, a new benzoxazinorifamycin, in rats and dogs
[J].
Hosoe, K
;
Mae, T
;
Konishi, E
;
Fujii, K
;
Yamashita, K
;
Yamane, T
;
Hidaka, T
;
Ohashi, T
.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,
1996, 40 (12)
:2749-2755

Hosoe, K
论文数: 0 引用数: 0
h-index: 0
机构:
KANEKA CORP, FINE CHEM RES LABS, TAKASAGO, HYOGO 676, JAPAN KANEKA CORP, FINE CHEM RES LABS, TAKASAGO, HYOGO 676, JAPAN

Mae, T
论文数: 0 引用数: 0
h-index: 0
机构:
KANEKA CORP, FINE CHEM RES LABS, TAKASAGO, HYOGO 676, JAPAN KANEKA CORP, FINE CHEM RES LABS, TAKASAGO, HYOGO 676, JAPAN

Konishi, E
论文数: 0 引用数: 0
h-index: 0
机构:
KANEKA CORP, FINE CHEM RES LABS, TAKASAGO, HYOGO 676, JAPAN KANEKA CORP, FINE CHEM RES LABS, TAKASAGO, HYOGO 676, JAPAN

Fujii, K
论文数: 0 引用数: 0
h-index: 0
机构:
KANEKA CORP, FINE CHEM RES LABS, TAKASAGO, HYOGO 676, JAPAN KANEKA CORP, FINE CHEM RES LABS, TAKASAGO, HYOGO 676, JAPAN

Yamashita, K
论文数: 0 引用数: 0
h-index: 0
机构:
KANEKA CORP, FINE CHEM RES LABS, TAKASAGO, HYOGO 676, JAPAN KANEKA CORP, FINE CHEM RES LABS, TAKASAGO, HYOGO 676, JAPAN

Yamane, T
论文数: 0 引用数: 0
h-index: 0
机构:
KANEKA CORP, FINE CHEM RES LABS, TAKASAGO, HYOGO 676, JAPAN KANEKA CORP, FINE CHEM RES LABS, TAKASAGO, HYOGO 676, JAPAN

Hidaka, T
论文数: 0 引用数: 0
h-index: 0
机构:
KANEKA CORP, FINE CHEM RES LABS, TAKASAGO, HYOGO 676, JAPAN KANEKA CORP, FINE CHEM RES LABS, TAKASAGO, HYOGO 676, JAPAN

Ohashi, T
论文数: 0 引用数: 0
h-index: 0
机构:
KANEKA CORP, FINE CHEM RES LABS, TAKASAGO, HYOGO 676, JAPAN KANEKA CORP, FINE CHEM RES LABS, TAKASAGO, HYOGO 676, JAPAN
[8]
Identification and antimicrobial activity of urinary metabolites of a rifamycin derivative in dog
[J].
Hosoe, K
;
Mae, T
;
Yamashita, K
;
Fujii, K
;
Yamane, T
;
Hidaka, T
;
Ohashi, T
.
XENOBIOTICA,
1996, 26 (03)
:321-332

Hosoe, K
论文数: 0 引用数: 0
h-index: 0
机构:
KANEKA CORP,FINE CHEM RES LABS,TAKASAGO,HYOGO 676,JAPAN KANEKA CORP,FINE CHEM RES LABS,TAKASAGO,HYOGO 676,JAPAN

Mae, T
论文数: 0 引用数: 0
h-index: 0
机构:
KANEKA CORP,FINE CHEM RES LABS,TAKASAGO,HYOGO 676,JAPAN KANEKA CORP,FINE CHEM RES LABS,TAKASAGO,HYOGO 676,JAPAN

Yamashita, K
论文数: 0 引用数: 0
h-index: 0
机构:
KANEKA CORP,FINE CHEM RES LABS,TAKASAGO,HYOGO 676,JAPAN KANEKA CORP,FINE CHEM RES LABS,TAKASAGO,HYOGO 676,JAPAN

Fujii, K
论文数: 0 引用数: 0
h-index: 0
机构:
KANEKA CORP,FINE CHEM RES LABS,TAKASAGO,HYOGO 676,JAPAN KANEKA CORP,FINE CHEM RES LABS,TAKASAGO,HYOGO 676,JAPAN

Yamane, T
论文数: 0 引用数: 0
h-index: 0
机构:
KANEKA CORP,FINE CHEM RES LABS,TAKASAGO,HYOGO 676,JAPAN KANEKA CORP,FINE CHEM RES LABS,TAKASAGO,HYOGO 676,JAPAN

Hidaka, T
论文数: 0 引用数: 0
h-index: 0
机构:
KANEKA CORP,FINE CHEM RES LABS,TAKASAGO,HYOGO 676,JAPAN KANEKA CORP,FINE CHEM RES LABS,TAKASAGO,HYOGO 676,JAPAN

Ohashi, T
论文数: 0 引用数: 0
h-index: 0
机构:
KANEKA CORP,FINE CHEM RES LABS,TAKASAGO,HYOGO 676,JAPAN KANEKA CORP,FINE CHEM RES LABS,TAKASAGO,HYOGO 676,JAPAN
[9]
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

Iatsimirskaia, E
论文数: 0 引用数: 0
h-index: 0
机构: Department of Pharmacology, Division of Clinical Pharmacology, Ohio State University, Columbus, OH

Tulebaev, S
论文数: 0 引用数: 0
h-index: 0
机构: Department of Pharmacology, Division of Clinical Pharmacology, Ohio State University, Columbus, OH

Storozhuk, E
论文数: 0 引用数: 0
h-index: 0
机构: Department of Pharmacology, Division of Clinical Pharmacology, Ohio State University, Columbus, OH

Utkin, I
论文数: 0 引用数: 0
h-index: 0
机构: Department of Pharmacology, Division of Clinical Pharmacology, Ohio State University, Columbus, OH

Smith, D
论文数: 0 引用数: 0
h-index: 0
机构: Department of Pharmacology, Division of Clinical Pharmacology, Ohio State University, Columbus, OH

Gerber, N
论文数: 0 引用数: 0
h-index: 0
机构: Department of Pharmacology, Division of Clinical Pharmacology, Ohio State University, Columbus, OH

Koudriakova, T
论文数: 0 引用数: 0
h-index: 0
机构: Department of Pharmacology, Division of Clinical Pharmacology, Ohio State University, Columbus, OH
[10]
HIV protease inhibitors, saquinavir, indinavir and ritonavir: Inhibition of CYP3A4-mediated metabolism of testosterone and binzoxazinorifamycin, KRM-1648, in human liver microsomes
[J].
Inaba, T
;
Fischer, NE
;
Riddick, DS
;
Stewart, DJ
;
Hidaka, T
.
TOXICOLOGY LETTERS,
1997, 93 (2-3)
:215-219

Inaba, T
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Toronto, Fac Med, Dept Pharmacol, Toronto, ON M5S 1A8, Canada Univ Toronto, Fac Med, Dept Pharmacol, Toronto, ON M5S 1A8, Canada

Fischer, NE
论文数: 0 引用数: 0
h-index: 0
机构: Univ Toronto, Fac Med, Dept Pharmacol, Toronto, ON M5S 1A8, Canada

Riddick, DS
论文数: 0 引用数: 0
h-index: 0
机构: Univ Toronto, Fac Med, Dept Pharmacol, Toronto, ON M5S 1A8, Canada

Stewart, DJ
论文数: 0 引用数: 0
h-index: 0
机构: Univ Toronto, Fac Med, Dept Pharmacol, Toronto, ON M5S 1A8, Canada

Hidaka, T
论文数: 0 引用数: 0
h-index: 0
机构: Univ Toronto, Fac Med, Dept Pharmacol, Toronto, ON M5S 1A8, Canada