PT - JOURNAL ARTICLE AU - WALTER G. LEVINE TI - HEPATIC UPTAKE, METABOLISM, AND BILIARY EXCRETION OF 7,12-DIMETHYLBENZANTHRACENE IN THE RAT DP - 1974 Mar 01 TA - Drug Metabolism and Disposition PG - 169--177 VI - 2 IP - 2 4099 - http://dmd.aspetjournals.org/content/2/2/169.short 4100 - http://dmd.aspetjournals.org/content/2/2/169.full SO - Drug Metab Dispos1974 Mar 01; 2 AB - After intravenous injection into rats, 3H-7,12-dimethylbenzanthracene is rapidly taken up by the liver, bound to particulate fractions, and subsequently converted to polar metabolites. These metabolites have far less affinity for particulate fractions than does the hydrocarbon and as a result they are recovered principally in the cytosol. After transfer to cytosol the metabolites are rapidly excreted in the bile. Agents that induce or inhibit the microsomal drug-metabolizing enzymes increase or decrease, respectively, the biliary excretion of metabolites after the injection of 3H-7,12-dimethylbenzanthracene. After the injection of metyrapone, an inhibition of biliary excretion is seen, although inhibition of metabolism of the hydrocarbon cannot be demonstrated using 10,000g liver supernatant fractions obtained from injected animals. Metabolism can be inhibited in vitro by metyrapone added directly to the incubation mixture in concentrations greater than 3 x 10 5 M. Injected metabolites of 3H-7,12-dimethylbenzanthracene appear to be taken up directly into the cytosol, and their rate of excretion is far more rapid than when the hydrocarbon itself is injected. Inducing and inhibiting agents do not affect the rate of biliary excretion of injected metabolites. It would appear that transfer into the cytosol is the final process before biliary excretion. The results suggest that this step is dependent upon metabolism which, under the conditions employed in this study, is probably the rate-limiting step in the overall biliary excretion mechanism. Copyright © 1974 by The American Society for Pharmacology and Experimental Therapeutics