title: Oral bioavailability and pharmacokinetics of elimination of 9-hydroxybenzo[a]pyrene and its glucoside and sulfate conjugates after administration to male and female American lobsters, Homarus americanus.
abstract: The pharmacokinetics of [(3)H]-9-hydroxybenzo[a]pyrene (9-OH-BaP), a highly lipophilic primary metabolite of benzo(a)pyrene, were examined after intrapericardial (iv) or oral doses of 50 or 200 microg/kg to intermolt American lobsters, Homarus americanus. Combining data for all lobsters, the average terminal elimination half-life of parent 9-OH-BaP was 97.3 h after iv and 56.5 h after oral administration, considerably less than found previously for benzo(a)pyrene (720 h). The oral bioavailability of parent 9-OH-BaP, calculated from the area under the hemolymph concentration curve, was 15.9%. The low bioavailability and variable elimination rates were attributed to extensive first-pass conjugation and sequestration in the hepatopancreas. BaP-9-sulfate was the major metabolite. Hemolymph concentrations of BaP-9-sulfate increased up to one day after the dose, and then decreased, with a terminal elimination half-life of 45 h. BaP 9-beta-D-glucoside was a minor metabolite in most hemolymph and tissue samples; an exception was hemolymph from the iv high-dose group. Concentrations of 9-OH-BaP and metabolites in the edible muscle tissue were similar to those in hemolymph, and 9-OH-BaP residues at 10 to 16 days after the dose were 3 to 12 ng/g muscle. Sulfotransferase and UDP-glucosyltransferase (UGT) activities with 9-OH-BaP were found in the antennal gland, intestinal mucosa, and hepatopancreas (UGT only). Sulfatase activity with BaP-9-sulfate, found in both the hepatopancreas and the antennal gland, was thought to contribute to metabolite cycling. These studies showed that 9-OH-BaP was readily conjugated to sulfate and glucose in the lobster, and that despite their high lipophilicity, 9-OH-BaP and conjugates were excreted from the lobster hemolymph and tissues much more rapidly than benzo[a]pyrene.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida 32610, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Li
authors.forename: M O
authors.initials: MO
authors.lastname: James
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001580:Benzopyrenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D001711:Biotransformation; D005260:Female; D005960:Glucosides / Q000378:metabolism; D006868:Hydrolysis; D007267:Injections; D008297:Male; D008121:Nephropidae / Q000378:metabolism*; D010496:Pericardium; D012727:Sex Characteristics; D013431:Sulfates / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D001580:Benzopyrenes; D005960:Glucosides; D013431:Sulfates; C021337:9-hydroxybenzo(a)pyrene