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.
1. The pharmacokinetics, disposition and bioavailability of nalidixic acid were examined in Rainbow Trout following i.v. and per os administration (5 mg/kg). 2. Nalidixic acid was biexponentially eliminated from plasma following i.v. dosing (t1/2 alpha = 0.06 h, t1/2 beta = 23.0 h). The volume of distribution (Vss) and total body clearance (Clb) were 964.7 ml/kg and 31.5 ml/kg/h, respectively. 3. In vitro plasma protein binding was specific and saturable over a range of concentrations from 0.43 microM to 20.0 mM. Binding was approx. 26% at kinetically relevant plasma concentrations. 4. Apparent oral bioavailability was determined to be > 100%, suggesting that nalidixic acid was largely bioavailable and non-linear pharmacokinetics were evoked. 5. Oral studies demonstrated the highest 14C nalidixic acid equivalent concentrations in bile, intestine and liver. Muscle contained intermediate concentrations but among all organs accounted for the greatest total amount of drug (12.2% of dose). Mass balance studies demonstrated composite values for per cent of dose administered of 23.7, 18.8, 8.5, 10.0, 7.4 and 2.3% for 1, 2, 3, 6, 9 and 15 days, respectively. 6. A glucuronic acid conjugate of nalidixic acid was identified by n.m.r. and mass spectral analysis as the single primary metabolite.
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