-transparent.png){kind=logo}
1. Caucasian liver samples were used in this study. N-demethylation of trimethadione (TMO) to dimethadione (DMO) was monitored in the presence of chemical inhibitors of CYPs, such as fluconazole, quinidine, dimethyl-nitrosamine, acetaminophen, phenacetin, chlorzoxazone and mephenytoin. Trimethadione N-demethylation was selectively inhibited by dimethylnitrosamine and chlorzoxazone (> 50%) and weakly inhibited by tolbutamide (12%) and fluconazole (22%), whereas other inhibitors showed no effect. This result suggested that TMO metabolism to DMO is mainly mediated by CYP2E1 and marginally by CYP2C and CYP3A4. 2. Fifteen human livers were screened and interindividual variability of TMO N-demethylation activity was 3-fold. Chlorzoxazone 6-hydroxylation activity was also measured and both activities were significantly correlated (r=0.735, p < 0.01). 3. DMO production by human cDNA expressed CYP enzymes was observed mainly for CYP2E1 (10.8 nmol/tube), marginally for CYP2C8 (0.22 nmol/tube) and not detectable for other CYP enzymes. 4. These results indicate that TMO metabolism is primarily catalysed by CYP2E1 and that trimethadione would be a suitable selective probe drug for the estimation of human CYP2E1 activity in vivo.
N Kurata, and
Y Nishimura, and
M Iwase, and
N E Fischer, and
B K Tang, and
T Inaba, and
H Yasuhara
July 2002,
Xenobiotica; the fate of foreign compounds in biological systems,
N Kurata, and
Y Nishimura, and
M Iwase, and
N E Fischer, and
B K Tang, and
T Inaba, and
H Yasuhara
November 1993,
Cancer research,
N Kurata, and
Y Nishimura, and
M Iwase, and
N E Fischer, and
B K Tang, and
T Inaba, and
H Yasuhara
October 1997,
Toxicology and applied pharmacology,
N Kurata, and
Y Nishimura, and
M Iwase, and
N E Fischer, and
B K Tang, and
T Inaba, and
H Yasuhara
December 2003,
Journal of clinical pharmacy and therapeutics,
N Kurata, and
Y Nishimura, and
M Iwase, and
N E Fischer, and
B K Tang, and
T Inaba, and
H Yasuhara
June 1998,
British journal of anaesthesia,
N Kurata, and
Y Nishimura, and
M Iwase, and
N E Fischer, and
B K Tang, and
T Inaba, and
H Yasuhara
October 2003,
Drug metabolism and disposition: the biological fate of chemicals,
N Kurata, and
Y Nishimura, and
M Iwase, and
N E Fischer, and
B K Tang, and
T Inaba, and
H Yasuhara
December 1995,
Drug metabolism and disposition: the biological fate of chemicals,
N Kurata, and
Y Nishimura, and
M Iwase, and
N E Fischer, and
B K Tang, and
T Inaba, and
H Yasuhara
December 2010,
Drug metabolism and disposition: the biological fate of chemicals,
N Kurata, and
Y Nishimura, and
M Iwase, and
N E Fischer, and
B K Tang, and
T Inaba, and
H Yasuhara
June 1996,
Pharmacogenetics,
N Kurata, and
Y Nishimura, and
M Iwase, and
N E Fischer, and
B K Tang, and
T Inaba, and
H Yasuhara
February 2001,
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association,
