Pharmaceutical industry investigators routinely evaluate the potential for a new drug to modify cytochrome p450 (p450) activities by determining the effect of the drug on in vitro probe reactions that represent activity of specific p450 enzymes. The in vitro findings obtained with one probe substrate are usually extrapolated to the compound's potential to affect all substrates of the same enzym...

It has been demonstrated that the activity of cytochrome P450 (CYP)3A4 in certain cases is stimulated by quinidine (positive heterotropic cooperativity). We report herein that the 4'- and 10-hydroxylation of S- and R-warfarin are enhanced in human liver microsomal incubations containing quinidine. These reactions were catalyzed by CYP3A4, based on data derived from immunoinhibitory studies, wit...

The major oxidation product of the classic polycyclic hydrocarbon carcinogen benzo(a)pyrene |B(a)P| is 3-hydroxy B(a)P. Numerous stud ies have been concerned with the measurement of B(a)P 3-hydroxylation activity in experimental animals and human tissues. Although human liver is the main site of this reaction, systematic studies had not been carried out to define the roles of individual cytochr...

Highly regioselective hydroxylation of propane at the terminal position has been achieved using CYP153A33 with decoy molecules. This combination can exhibit ability to hydroxylate ethane and methane.

Omeprazole 5-hydroxylation and sulfoxidation activities were determined in liver microsomes of different humans whose levels of individual forms of cytochrome P450 (P450 or CYP) varied. Correlation coefficients between omeprazole 5-hydroxylation activities (when determined at a substrate concentration of 10 microM) and S-mephenytoin 4'-hydroxylation and testosterone 6beta-hydroxylation activiti...

In vitro studies were conducted to identify the hepatic cytochrome P450 (CYP) forms involved in the oxidative metabolism of [14C]ABT-761 and its N-dehydroxylated metabolite, [14C]ABT-438, by human liver microsomes. The two compounds were metabolized by parallel pathways, to form the corresponding methylene bridge hydroxy metabolites. There was no evidence of sulfoxidation and/or ring hydroxylat...

The metabolism of some steroids has been investigated in liver microsomal preparations from male germ-free and conventional rats. Hydroxylation of 4-[4-14C]androstene3,17-dione in positions 60 and 16~~ is about 2 and 1.5 times more efficient in germ-free than in conventional rats. The same is true for 6/3and Zol-hydroxylation of 4-[4J4C]pregnene-3,20-dione (about 1.6 and 1.2 times larger, respe...