Induction of diphenytriazol on cytochrome CYP1A.
OBJECTIVE
To study the effects of diphenytriazol on cytochrome P-450 (CYP) enzymes.


METHODS
SD rats were pretreated with diphenytriazol. The catalytic activities of rat liver microsomes were determined by assaying ethoxyresorufin-O-deethylase (EROD) and pentoxyresorufin-O-dealkylase. Phenacetin and aminopyrine were selected as the substrate of CYP1A and CYP2B, respectively. The concentration of remaining substrate in microsomal incubates was determined by reversed-phase high-performance liquid chromatography (RP-HPLC). The inhibition of fluvoxamine or alpha-naphthoflavone on phenacetin metabolism was measured.


RESULTS
Phenacetin was significantly metabolized in the diphenytriazol-treated microsomes and the metabolic degree increased according to the diphenytriazol-treatment days. There existed a significant correlation between the metabolic degree of phenacetin and EROD in the microsomes pretreated with diphenytriazol. Both fluvoxamine and alpha-naphthoflavone inhibited the metabolism of phenacetin significantly, and the inhibition constants (K(i)) were (5.4+/-1.0) micromol/L and (10.4+/-0.5) micromol/L, respectively. The activity of microsomes pretreated with diphenytriazol for 4 d was similar to that in b-naphthoflavone group, but was significantly different from those in control group and phenobarbital group.


CONCLUSIONS
These results reveal that diphenytriazol is a novel inducer of CYP1A.
Hu
Yun-zhen
YZ
Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, China.
Yao
Tong-wei
TW
D000020:Abortifacient Agents, Nonsteroidal / Q000494:pharmacology; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D005260:Female; D016666:Fluvoxamine / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism*; D010615:Phenacetin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology*; D019324:beta-Naphthoflavone / Q000494:pharmacology
D000020:Abortifacient Agents, Nonsteroidal; D001571:Benzoflavones; D014230:Triazoles; D000632:Aminopyrine; C011512:alpha-naphthoflavone; D019324:beta-Naphthoflavone; C030266:3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D010615:Phenacetin; D016666:Fluvoxamine