PHARMACOKINETIC AND EFFICACY STUDIES ON BATH-ADMINISTERING POTENTIATED SULFONAMIDES IN ATLANTIC HALIBUT, HIPPOGLOSSUS-HIPPOGLOSSUS L

Citation
Ob. Samuelsen et al., PHARMACOKINETIC AND EFFICACY STUDIES ON BATH-ADMINISTERING POTENTIATED SULFONAMIDES IN ATLANTIC HALIBUT, HIPPOGLOSSUS-HIPPOGLOSSUS L, Journal of fish diseases, 20(4), 1997, pp. 287-296
Citations number
29
Categorie Soggetti
Marine & Freshwater Biology",Fisheries
Journal title
ISSN journal
01407775
Volume
20
Issue
4
Year of publication
1997
Pages
287 - 296
Database
ISI
SICI code
0140-7775(1997)20:4<287:PAESOB>2.0.ZU;2-Q
Abstract
The uptake, metabolism, tissue distribution and excretion of four sulp honamides and trimethoprim following bath treatment of Atlantic halibu t, Hippoglossus hippoglossus L., were studied. Bath treatment using a concentration of 200 mu g ml(-1) for 72 h resulted in peak sulphadimid ine concentrations in muscle and abdominal organ homogenates of 32.6 a nd 68.2 mu g g(-1), respectively. The corresponding values were 24.4 a nd 73.4 mu g g(-1) for sulphaguanidine, 6.1 and 45.1 mu g g(-1) for su lphamethoxazole, 2.1 adn 15.1 mu g g(-1) for for trimethoprim. After a 72-h treatment, approximately 90% of the sulphadimethoxine and sulpha methoxazole present in tissues was found as the N-4-acetylated metabol ite, whereas for sulphadimidine and sulphaguanidine, the N-4-acetylati ons were from 9 to 23%. Based on these preliminary absorption studies, sulphadimidine was chosen as the companion sulphonamide to trimethopr im. Using a combination of 500 mu g ml(-1) sulphadimidine and 100 mu g ml(-1) trimethoprim in the bath for 72 h, peak muscle and liver conce ntrations of 262 and 312 mu g g(-1), respectively, for sulphadimidine and 32.8 and 83.6 mu g g(-1), respectively, for trimerhoprim were achi eved. Elimination hall-lives (t(1/2)beta) for sulphadimidine were calc ulated to be 35 and 48 h for muscle and liver, respectively. The corre sponding values for 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 mu g g(-1) for trimethoprim and 0.1 mu g g(-1) for sulphadimidine, the elimination times (E-t95) f or muscle and liver were calculated to be 18 and 26 days, respectively , for sulphadimidine and 40 and 55 days, respectively, for trimethopri m. Minimum inhibitory concentrations (MIC) values against selected str ains of Vibrio sp. were equal to or above 128 mu g ml(-1) for sulphadi midine, between 0.25 and 4.00 mu g ml(-1) for trimethoprim and between 0.4 and 8.8 mu g ml(-1) for various ratios of the sulphadimidine:trim ethoprim combination. In the tested ratios, the combined antimicrobial action of trimethoprim and sulphadimidine were synergistic, as reveal ed by their fractional inhibitory concentration (FIC) indices. In gene ral, the 1:5 trimethoprim sulphadimidine ratio showed the highest degr ee of synergism. Using a combination of 500 mu g ml(-1) sulphadimidine and 100 mu g ml(-1) trimethoprim in the bath for 72 h, concentrations greater than a MIC value of 0.8 mu g ml(-1) were maintained for 22 da ys in muscle and 29 days in liver. In a laboratory challenge experimen t using Vibrio anguillarum strain HI 11347, a significantly lower mort ality was observed in the drug-treated group (40%) compared to the unt reated control group (93%).