Single-dose pharmacokinetic study of oxolinic acid and vetoquinol, an oxolinic acid ester, in Atlantic salmon (Salmo salar) held in seawater and in vitro antibacterial activity against Aeromonas salmonicida

The pharmacokinetic properties of the antibacterial agent oxolinic acid and its carbitol ester (Vetoquinol) were studied after intravenous (oxolinic acid) and oral (oxolinic acid and Vetoquinol) administration to Atlantic salmon (Salmo salar) held in seawater at 10 degrees C. Following intravenous injection of oxolinic acid, the plasma drug concentration-time profile showed two distinct phases. The distribution half life (t1/2 alpha) was calculated to be 1 h and the elimination half life (t1/2beta) to be 15 h. Total body clearance (Cl(T)) was determined to be 0.40 l/kg h and the volume of distribution at steady state, Vd(ss) to be 5.7 l/kg indicating good tissue penetration of oxolinic acid in Atlantic salmon. The peak plasma concentrations (C(max)) and the time to peak plasma concentrations (T(max)) for oxolinic acid were estimated to be 0.5 microgram/ml and 19 h, respectively, when administrating oxolinic acid and 3.8 microgram/ml and 7 h, respectively, following oral administration of Vetoquinol. A bioavailability of 25% was calculated following oral administration of oxolinic acid whereas a total bioavailability of 93% (oxolinic acid + Vetoquinol) where oxolinic acid accounted for 71% was calculated following oral administration of Vetoquinol. In muscle, C(max) and T(max) were estimated to 3.2 microgram/g and 17 h, respectively, following oral administration of oxolinic acid with corresponding values of 4.6 microgram/g and 14 h for oxolinic acid following oral administration of Vetoquinol. Following oral administration of oxolinic acid, C(max) and T(max) were estimated to 5.6 microgram/g and 10 h, respectively, in liver with corresponding values of 11.5 microgram/g and 9 h following oral administration of Vetoquinol The in vitro minimum inhibitory concentration (MIC) values for oxolinic acid and Vetoquinol against 20 strains of Aeromonas salmonicida ranged from 0.0625 to > 8 microgram/ml for oxolinic acid and from 2 to > 516 microgram/ml for Vetoquinol.