PMID: 8591690Jan 1, 1995Paper

Factors involved in the N-oxidation of isomeric aromatic diazines by microsomal preparations

Drug Metabolism and Drug Interactions
T G Altuntas, J W Gorrod

Abstract

Factors affecting the metabolism of isomeric aromatic diazines in vitro were studied and the conditions which allow maximal metabolism established. The N-oxidation of isomeric diazines was linear with respect to microsomal concentration up to 0.5 g original liver weight per ml using a rabbit microsomal suspension. N-Oxidation was also linear up to between 20-30 minutes depending on substrate studied. The rate of N-oxide production increased with increase in substrate concentration up to about 10 mumol/incubate, after which the rate declined. By using the data obtained the appropriate kinetic factors, Km and Vmax, for the N-oxidation of pyrazine, pyrimidine and pyridazine by rabbit hepatic microsomal preparations were calculated. Spectral binding constants, Ks, of substrates to cytochrome P450 were also calculated and appeared to be related to the Km values.

References

Apr 1, 1979·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·J W Gorrod, L A Damani
Jan 1, 1978·Methods in Enzymology·J B Schenkman, D L Cinti
Oct 1, 1987·European Journal of Drug Metabolism and Pharmacokinetics·P J Watkins, J W Gorrod
Oct 1, 1987·European Journal of Drug Metabolism and Pharmacokinetics·K el-Ghomari, J W Gorrod
Jul 1, 1971·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·J W Gorrod
Jul 1, 1971·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·J D Phillipson
Jan 1, 1984·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·G G Gibson, P P Tamburini

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