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A single‐dose pharmacokinetic study of oxolinic acid and vetoquinol, an oxolinic acid ester, in Atlantic halibut, Hippoglossus hippoglossus L., held in sea water at 9 °C
Author(s) -
Samuelsen O. B.,
Ervik A.
Publication year - 1999
Publication title -
journal of fish diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.819
H-Index - 85
eISSN - 1365-2761
pISSN - 0140-7775
DOI - 10.1046/j.1365-2761.1999.00133.x
Subject(s) - hippoglossus hippoglossus , oxolinic acid , halibut , pharmacokinetics , bioavailability , minimum inhibitory concentration , volume of distribution , biology , chromatography , chemistry , intraperitoneal injection , pharmacology , biochemistry , fishery , antibiotics , nalidixic acid , antibiotic resistance , fish <actinopterygii>
The pharmacokinetic properties of the antibacterial agent oxolinic acid were studied after intravenous, intraperitoneal and oral administration to 1.5–3.0 kg Atlantic halibut, Hippoglossus hippoglossus L., held in sea water at 9 °C. Following intravenous injection, the plasma drug concentration‐time profile showed two distinct phases. The terminal elimination half‐life was estimated to be 52 h, whereas total body clearance (Cl T ) was determined to be 0.044 L kg –1 h –1 . The volume of distribution at steady state, V d(ss) , was calculated to be 3.0 L kg –1 , indicating good tissue penetration of oxolinic acid in Atlantic halibut. The peak plasma concentration (C max ) and the time to peak plasma concentration (T max ) were estimated to be 1.2 and 2.7 μg mL –1 , and 21.5 and 80 h, respectively, following oral administration of medicated feed or intraperitoneal injection. The corresponding bioavailabilities were calculated to be 15% and 92%, respectively. Oral administration of vetoquinol, the carbitol ester of oxolinic acid, increased the bioavailability of oxolinic acid to 64% and the total bioavailability (oxolinic acid + vetoquinol) to 82%, whereas C max and T max values of 6.7 μg mL –1 and 14.5 h, respectively, for oxolinic acid, and 1.0 μg mL –1 and 6.3 h, respectively, for vetoquinol were obtained. Based on a minimum inhibitory concentration (MIC) of 0.0625 μg mL –1 for susceptible strains, a single intraperitoneal injection of 25 mg kg –1 of oxolinic acid maintains plasma levels in excess of 0.25 μg mL –1 , corresponding to four times the MIC value, for ≈12 days. The corresponding values for a single oral dose of 25 mg kg –1 of oxolinic acid and vetoquinol were 5 and 10 days, respectively. For resistant strains with a MIC of 1 μg mL –1 , a single oral dose of vetoquinol (25 mg kg –1 ) maintained plasma levels in excess of 4 μg mL –1 for 34 h.