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The pharmacokinetics, bioavailability, and disposition of oxolinic acid (OA), a quinolone antibacterial drug, were examined in a warmwater (channel catfish (Ictalurus punctatus)) and coldwater fish species (rainbow trout (Oncorhynchus mykiss)). Studies were performed at 24 and 14 °C for catfish and at 14 °C for trout to compare temperature- and species-related differences. Analysis of OA pharmacokinetics when determined by HPLC provided elimination half-life [Formula: see text], volume of distribution (Vss), and clearance (Clb) estimates for 24 °C catfish, 14 °C catfish, and 14 °C trout of 40.9, 69.3, and 81.3 h, 939, 880, and 1817 mL/kg, and 16.3, 8.9, and 16.9 mL∙kg∙h−1, respectively. Following oral administration, OA plasma concentrations peaked between 8 and 24 h for all treatments; however, 14 °C trout and 14 °C catfish sustained peak concentrations for a longer duration than 24 °C catfish. Oral OA bioavailabilities were 56.0, 91.8, and 90.7% for 24 °C catfish, 14 °C catfish, and 14 °C trout, respectively. OA distribution data for muscle of 14 °C catfish demonstrated an inordinately high peak concentration and delayed time to peak relative to other treatments. Elimination half-lives of OA in muscle were 33.1, 54.3, and 141 h for 24 °C catfish, 14 °C catfish, and 14 °C trout, respectively.

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In the aquatic environment, diet is an important route of exposure for the common contaminant and procarcinogen benzo(a)pyrene (BaP). Dietary organisms var'yin their BaP content and in contaminated areas often contain other xenobiotics including cytochrome P4501A inducers.This study eamined the effect of dose and previous dietary exposure to the inducer 3-naphthoflavone (BNF) upon the intestinal metabolism of BaP and the sptemic bioavailability of BaP-derived products in catfish. BaP was administered at 2 and 20 pM into in situ-isolated perflsed intestines of control and BNF-pretreated catfish. The intestine formed an array of metabolites in all treatments including potentially hazardous metabolites such as BaP-7,8 and 9,10 dihydrodiols and 6-methy-BaP. BNF treatment disproportionally increased the contribution of BaP-7,8 and 9,10 dihydrodiols relative to the contributions of other metabolites. A greater percentage of metabolites was evident as conjugates in 2 pM controls, whereas a greater percentage of unconjugated metabolites was evident for 20 pM controls and BNF treatments of both dosages. BNF pretreatment and the higher 20 pM BaP dose resulted in greater bioavailabilit4 with 2.6-5.5-fold and 3.0-6.3-fold s in temically avhlable BaP products, respectively.Metabolites represented 10.2-23.1% of the increased bioavilability with BNF treatment, saggesting that mechanisms, in addition to induced metabolism, may be operative. These results indicate that intestnal bioavailability, level of biotransformation, and the metabolic profile of BaP-derived products entering the bloed from the intestine may be altered by dose and dietary BNF pretreatment.

Biotransformation of xenobiotics in fish occurs by many of the same reactions as in mammals. These reactions have been shown to affect the bioaccumulation, persistence, residue dynamics, and toxicity of select chemicals in fish. P-450-dependent monooxygenase activity of fish can be induced by polycyclic aromatic hydrocarbons, but phenobarbital-type agents induce poorly, if at all. Fish monooxygenase activity exhibits ideal temperature compensation and sex-related variation. Induction of monooxygenase activity by polycyclic aromatic hydrocarbons can result in qualitative as well as quantitative changes in the metabolic profile of a chemical. Induction can also alter toxicity. In addition, multiple P-450 isozymes have been described for several fish species. The biotransformation products of certain chemicals have been related to specific P-450 isozymes, and the formation of these products can be influenced by induction. Exposure of fish to low levels of certain environmental contaminants has resulted in induction of specific monooxygenase activities and monitoring of such activities has been suggested as a means of identifying areas of pollutant exposure in the wild.

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