H. Jarboe et al., PHARMACOKINETICS, BIOAVAILABILITY, PLASMA-PROTEIN BINDING AND DISPOSITION OF NALIDIXIC-ACID IN RAINBOW-TROUT (ONCORHYNCHUS-MYKISS), Xenobiotica, 23(9), 1993, pp. 961-972
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.