RT Journal Article SR Electronic T1 Metabolism and Disposition of [14C]1-Nitronaphthalene in Male Sprague-Dawley Rats JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 1456 OP 1465 VO 27 IS 12 A1 Jason S. Halladay A1 John-Michael Sauer A1 I. Glenn Sipes YR 1999 UL http://dmd.aspetjournals.org/content/27/12/1456.abstract AB In rats and mice, 1-nitronaphthalene (1-NN) produces both lung and liver toxicity. Even though these toxicities have been reported, the metabolism and disposition of 1-NN have not been elucidated. Therefore, studies were performed to characterize its fate after i.p. and i.v. administration to male Sprague-Dawley rats. After i.p. administration of [14C]1-NN (100 mg/kg; 60 μCi/kg), 84% of the dose was eliminated in the urine and feces by 48 h. At 96 h, 60% of the dose was recovered in the urine, 32% in the feces, and 1% collectively in the tissues, blood, and gastrointestinal contents. The terminal phase rate constant (kterm) of 1-NN was 0.21 h−1, the terminal phase half-life (T1/2,term) was 3.40 h, and the systemic bioavailability was 0.67. When administered i.v. (10 mg/kg; 120 μCi/kg), 85% of the dose was eliminated in the urine and feces by 24 h. At the end of the study (96 h), 56% of the dose was recovered in the urine, 36% in the feces, and 1% collectively in the tissues, blood, and gastrointestinal contents. Interestingly, 88% of the dose was secreted into bile by 8 h. Thekterm was 0.94 h−1 and theT1/2,term was 0.77 h. The major urinary metabolite after both routes of administration wasN-acetyl-S-(hydroxy-1-nitro-dihydronaphthalene)-l-cysteine. Other urinary metabolites identified include hydroxylated, dihydroxylated, glucuronidated, sulfated, and reduced metabolites, as well as dihydrodiol. The major biliary metabolite was hydroxy-glutathionyl-1-nitro-dihydronaphthalene. These data show that 1-NN undergoes extensive metabolism and enterohepatic recirculation, and the majority of the dose is eliminated in the urine. The American Society for Pharmacology and Experimental Therapeutics