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.

The complete analysis of oxytetracycline pharmacokinetics in farmed Pacific white shrimp (Litopenaeus vannamei)

“…As there are significant differences in physiological rates associated with the major moulting stages, crustacean physiological studies generally suggest that animals in one or another stage of the moulting cycle (intermoult) be used only when they are in physiological equilibrium (Carvalho & Phan, 1998). For example, Li and James (2000) standardized their samples by using intermoult stage lobsters. However, there have been no known sample standardizations previously in pharmacokinetic studies of culture shrimps (Park et al.…”

“…when they are in physiological equilibrium (Carvalho & Phan, 1998). For example, Li and James (2000) standardized their samples by using intermoult stage lobsters. However, there have been no known sample standardizations previously in pharmacokinetic studies of culture shrimps (Park et al, 1995;Reed et al, 2004;Sangrungruang et al, 2004;Uno, 2004), and these studies all show considerable variability in hemolymph drug concentrations.…”

1-Hydroxypyrene Glucuronide as the Major Aqueous Pyrene Metabolite in Tissue and Gut Fluid From the Marine Deposit-Feeding Polychaete Nereis Diversicolor

“…Though based on a triplicate measure of the pooled gut fluid sample, the mass balance for gut fluid presented here seems only to suggest that the relative distribution of pyrene-derived compounds in gut fluid resembles that of tissue. In a study of 9-OH-BaP, a highly lipophilic primary metabolite of BaP, in American lobster (Homarus americanus), Li and James [35] found that 9-OH-BaP was readily conjugated to sulfate and glucose and that, despite its high lipophilicity, 9-OH-BaP was excreted from the lobster hemolymph and tissue much more rapidly than BaP. More studies concerning the pharmacokinetics of hydroxylated PAH and their metabolic conjugates in individual animals are needed to identify if this holds true in tissue and gut fluid of deposit-feeding marine invertebrates.…”

Sex steroids and potential mechanisms of non-genomic endocrine disruption in invertebrates

“…Identification of these compounds was based on their susceptibility to hydrolysis by sulfatases. Few studies have measured in vitro sulfation in crustaceans (Li and James 2000;de Knecht et al 2001). In vitro sulfation of steroid hormones occurs at rather highmetabolic rates in echinoderms, but not in molluscs or crustaceans (Janer et al 2005c).…”