Pharmacokinetic and efficacy studies on bath-administering potentiated sulphonamides in Atlantic halibut, Hippoglossus hippoglossus L.
Article first published online: 31 OCT 2003
Blackwell Science Ltd, Oxford
Journal of Fish Diseases
Volume 20, Issue 4, pages 287–296, July 1997
How to Cite
Samuelsen, O.B., Lunestad, B.T. and Jelmert, A. (1997), Pharmacokinetic and efficacy studies on bath-administering potentiated sulphonamides in Atlantic halibut, Hippoglossus hippoglossus L. Journal of Fish Diseases, 20: 287–296. doi: 10.1046/j.1365-2761.1997.00294.x
- Issue published online: 31 OCT 2003
- Article first published online: 31 OCT 2003
- Cited By
The uptake, metabolism, tissue distribution and excretion of four sulphonamides and trimethoprim following bath treatment of Atlantic halibut, Hippoglossus hippoglossus L., were studied. Bath treatment using a concentration of 200 μg ml–1 for 72 h resulted in peak sulphadimidine concentrations in muscle and abdominal organ homogenates of 32·6 and 68·2 μg g–1, respectively. The corresponding values were 24·4 and 73·4 μg g–1 for sulphaguanidine, 6·1 and 45·1 μg g–1 for sulphamethoxazole, 2·1 and 15·1 μg g–1 for sulphadimethoxine, and 99 and 169 μg g–1 for trimethoprim. After a 72-h treatment, approximately 90% of the sulphadimethoxine and sulphamethoxazole present in tissues was found as the N4-acetylated metabolite, whereas for sulphadimidine and sulphaguanidine, the N4-acetylations were from 9 to 23%. Based on these preliminary absorption studies, sulphadimidine was chosen as the companion sulphonamide to trimethoprim. Using a combination of 500 μg ml–1 sulphadimidine and 100 μg ml–1 trimethoprim in the bath for 72 h, peak muscle and liver concentrations of 262 and 312 μg g–1, respectively, for sulphadimidine and 32·8 and 83·6 μg g–1, respectively, for trimethoprim were achieved. Elimination half-lives (t1/2β) for sulphadimidine were calculated to be 35 and 48 h for muscle and liver, respectively. The corresponding values for trimethoprim were 98 and 116 h. Using the 95% confidence limit for single observations (95% prediction limit) and a maximum residue limit (MRL) value of 0·05 μg g–1 for trimethoprim and 0·1 μg g–1 for sulphadimidine, the elimination times (Et95) for muscle and liver were calculated to be 18 and 26 days, respectively, for sulphadimidine and 40 and 55 days, respectively, for trimethoprim. Minimum inhibitory concentrations (MIC) values against selected strains of Vibrio sp. were equal to or above 128 μg ml–1 for sulphadimidine, between 0·25 and 4·00 μg ml–1 for trimethoprim and between 0·4 and 8·8 μg ml–1 for various ratios of the sulphadimidine:trimethoprim combination. In the tested ratios, the combined antimicrobial action of trimethoprim and sulphadimidine were synergistic, as revealed by their fractional inhibitory concentration (FIC) indices. In general, the 1:5 trimethoprim sulphadimidine ratio showed the highest degree of synergism. Using a combination of 500 μg ml–1 sulphadimidine and 100 μg ml–1 trimethoprim in the bath for 72 h, concentrations greater than a MIC value of 0·8 μg ml–1 were maintained for 22 days in muscle and 29 days in liver. In a laboratory challenge experiment using Vibrio anguillarum strain HI 11347, a significantly lower mortality was observed in the drug-treated group (40%) compared to the untreated control group (93%).