Disposition of 1-naphthol in the channel catfish (Ictalurus punctatus).
The pharmacokinetics, tissue distribution, and metabolism of 1-naphthol were examined in the channel catfish (Ictalurus punctatus). Catfish were administered [1-14C]1-naphthol intravascularly at 1, 5, or 25 mg/kg or orally at 1 mg/kg. Plasma data for 1-naphthol were fitted by a three-compartment pharmacokinetic model. There were dose-related changes in the area under the plasma concentration vs. time curve, apparent volume of distribution, and total body clearance after intravascular dosing. After oral dosing, peak plasma concentrations of 1-naphthol occurred at 1 hr; parent compound made up less than 15% of the total radioactivity, and the bioavailability was 32%. Plasma protein binding was 92% and was independent of concentration. 1-Naphthol and metabolites were rapidly eliminated from the tissues after oral dosing; less than 1% of the administered dose remained at 24 hr. Renal excretion was the primary route of elimination of total 14C. Approximately 60% of the oral dose was excreted in the urine within 48 hr. Parent 1-naphthol made up 1% of the urinary 14C. Major metabolites in the urine were sulfate and glucuronide conjugates, which composed 65 and 28% of the total 14C, respectively. Biliary excretion accounted for 7% of the oral dose. The glucuronide conjugate and an unidentified polar metabolite made up the majority of the biliary 14C. The high capacity of channel catfish for conjugative metabolism of 1-naphthol was demonstrated. The dose dependency of pharmacokinetic values could not be explained by saturable metabolism or plasma protein binding.
Stehly
G R
GR
U.S. Food and Drug Administration, Fishery Research Branch, Dauphin Island, AL 36528.
Plakas
S M
SM
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D007059:Ictaluridae; D008657:Metabolic Clearance Rate; D009284:Naphthols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution / Q000187:drug effects
D009284:Naphthols; C029350:1-naphthol