A single-dose pharmacokinetic study of oxolinic acid and vetoquinol, an oxolinic acid ester, in cod, Gadus morhua L., held in sea water at 8 degrees C and in vitro antibacterial activity of oxolinic acid against Vibrio anguillarum strains isolated fr

摘要

The pharmacokinetic properties of the antibacterial agent oxolinic acid and vetoquinol, the carbitol ester of oxolinic acid, were studied after intravenous (i.v.) and oral (p.o.) administration to 100-150 g cod, Gadus morhua L., held in sea water at 8 degreesC. Following i.v. injection, the plasma drug concentration-time profile showed two distinct phases. The distribution half-life (t(1/2)alpha) was estimated at 1.3 h, the elimination half-life (t(1/2)beta) as 84 h and the total body clearance (Cl-T) as 0.047 L kg(-1) h(-1). The volume of distribution at steady state, V-d(ss) was calculated to be 5.5 L kg(-1) , indicating good tissue penetration of oxolinic acid in cod. Following p.o. administration of oxolinic acid or vetoquinol, the peak plasma concentrations (C-max) of oxolinic acid and the time to peak plasma concentrations (T-max) were estimated to be 1.2 and 2.5 mug mL(-1), and 24 and 12 h, respectively. The bioavailabilities of oxolinic acid following p.o. administration of oxolinic acid and vetoquinol were calculated to be 55 and 72%, respectively. The in vitro minimum inhibitory concentration (MIC) values of oxolinic acid against three strains of Vibrio anguillarum isolated from diseased cod were 0.016 mug mL(-1) (HI-610), 0.250 mug mL(-1) (HI-618) and 0.250 mug mL(-1) (HI-A21). Based on a MIC value of 0.016 mug mL(-1) a single p.o. administration of 25 mg kg(-1) of oxolinic acid maintains plasma levels in excess of 0.064 mug mL(-1), corresponding to four times the MIC-value, for approximately 12 days. The analogous value for a single p.o. dose of 25 mg kg(-1) of oxolinic acid administered as vetoquinol was 13 days.