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The metabolism and disposition of 3,4,4′-trichlorocarbanilide in the intact and bile duct-cannulated adult and in the newborn rhesus monkey (M. mulatta)

Authors
Journal
Toxicology and Applied Pharmacology
0041-008X
Publisher
Elsevier
Publication Date
Volume
46
Issue
3
Identifiers
DOI: 10.1016/0041-008x(78)90306-x

Abstract

Abstract The metabolism and disposition of intravenously infused radioactive 3,4,4′-trichloro[ 14C]carbanilide (TCC) in the adult and newborn rhesus monkey have been evaluated. In adult animals the major metabolic reactions were N-glucuronide formation or ring hydroxylation followed by conjugation to glucuronic acid or sulfuric acid. Removal of 14C from the plasma was biphasic; TCC and the N-glucuronides accounted for the fast phase, and the O-sulfate conjugates accounted for the slow phase. The major urinary metabolites were the N-glucuronides of TCC. The tissue residue of 14C was low in the monkeys and was limited primarily to tissues that are active in drug metabolism (liver, kidneys, and lungs). The bile was the major route of elimination with glucuronide conjugates as the major radioactive component. Enterohepatic circulation was extensive but did not affect the plasma concentrations or the elimination kinetics of TCC-derived material from the plasma. The newborn monkey also metabolized TCC by ring hydroxylation or N-glucuronidation. The plasma kinetics were similar to those observed in adults as was the tissue distribution. Unlike the adult, there were only very low amounts of O-glucuronides and, instead, high amounts of O-sulfate conjugates. It is concluded that the infant monkey can readily metabolize and eliminate TCC.

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