PHARMACOKINETICS, BIOAVAILABILITY, PLASMA-PROTEIN BINDING AND DISPOSITION OF NALIDIXIC-ACID IN RAINBOW-TROUT (ONCORHYNCHUS-MYKISS)

1. The pharmacokinetics, disposition and bioavailability of nalidixic acid were examined in Rainbow Trout following i.v. and per os administ ration (5 mg/kg). 2. Nalidixic acid was biexponentially eliminated fro m plasma following i.v. dosing (t1/2alpha = 0.06 h, t1/2beta = 23.0 h) . The volume of distribution (V(ss)) and total body clearance (Cl(b)) were 964.7 ml/kg and 31.5 ml/kg/h, respectively. 3. In vitro plasma pr otein binding was specific and saturable over a range of concentration s from 0.43 mum to 20.0 mM. Binding was approx. 26% at kinetically rel evant plasma concentrations. 4. Apparent oral bioavailability was dete rmined to be > 100%, suggesting that nalidixic acid was largely bioava ilable and non-linear pharmacokinetics were evoked. 5. Oral studies de monstrated the highest C-14 nalidixic acid equivalent concentrations i n bile, intestine and liver. Muscle contained intermediate concentrati ons but among all organs accounted for the greatest total amount of dr ug (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.