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 °C and in vitro antibacterial activity of oxolinic acid against Vibrio anguillarum strains isolated from diseased cod

• Published in: Journal of Fish Diseases
• Main Authors: Samuelsen, O B, Bergh, Ø, Ervik, A
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2003
• Subjects: Gadus morhua
• Online Access: http://dx.doi.org/10.1046/j.1365-2761.2003.00466.x; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1046%2Fj.1365-2761.2003.00466.x; https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2761.2003.00466.x

Abstract 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 °C. Following i.v. injection, the plasma drug concentration‐time profile showed two distinct phases. The distribution half‐life ( t 1/2 α ) was estimated at 1.3 h, the elimination half‐life ( t 1/2 β ) 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 μg 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 μg mL −1 (HI‐610), 0.250 μg mL −1 (HI‐618) and 0.250 μg mL −1 (HI‐A21). Based on a MIC value of 0.016 μg mL −1 a single p.o. administration of 25 mg kg −1 of oxolinic acid maintains plasma levels in excess of 0.064 μg 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.