@article {Mehendale124, author = {H M Mehendale}, title = {Uptake and disposition of chlorinated biphenyls by isolated perfused rat liver.}, volume = {4}, number = {2}, pages = {124--132}, year = {1976}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The hepatic disposition of four chlorinated biphenyls was studied in isolated perfused rat liver preparations perfused with 30\% rat blood. Biliary excretion of 14C-labeled 4-chlorobiphenyl (1-CB): 4,4{\textquoteright}-dichlorobiphenyl (2-CB): 2,4,5,2{\textquoteright},5{\textquoteright}-pentachlorobiphenyl (5-CB) and 2,4,5,2{\textquoteright},5{\textquoteright}-hexachlorobiphenyl (6-CB) appeared to be inversely related to increased chlorination. Each of the compounds was rapidly taken up by the liver from the circulating perfusate. After 4 hr of perfusion, biliary excretion of 14C from 1-CB, 2-CB, 5-CB, and 6-CB was 48.2, 29.6, 20.5, and 1.3\% of total dose, respectively. For 1-CB, this rate of biliary elimination represents a maximum perfusate/bile ratio of 107. About 97\% of the label in the bile from 1-CB experiments was in the form of metabolites. Biliary excretion of 1-CB was biphasic: an initial rapid phase (t 1/2 = 13 min) was followed by a slower second phase (t 1/2 = 122 min). When the metabolites of 1-CB were added to the perfusate, biliary excretion of these metabolites was monophasic; t 1/2 = 120 min, which corresponded to the slower phase observed when the parent compound was presented to the liver. 1-CB disappeared from the perfusate via a biphasic process. Metabolites of 1-CB effused into the perfusate immediately after the initial rapid uptake of 1-CB by the liver, and the recirculating pool of metabolites was eliminated in the bile by the slow postsynthetic phase of biliary elimination. Less than 2\% of 1-CB was present as the parent compound in the perfusion system after 4 hr of perfusion. These findings indicate that the metabolism of 1-CB is not the limiting factor in the hepatic disposition of 1-CB and that the circulating metabolites of 1-CB effusing from the liver might be the major source for urinary excretion.}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/4/2/124}, eprint = {https://dmd.aspetjournals.org/content/4/2/124.full.pdf}, journal = {Drug Metabolism and Disposition} }