POTENTIATED SULFONAMIDES - IN-VITRO INHIBITORY EFFECT AND PHARMACOKINETIC PROPERTIES IN ATLANTIC SALMON IN SEAWATER

The in vitro antibacterial activities of one sulfadimethoxine-ormetopr im (SMX-OMP) and two sulfadiazine-trimethoprim (SDZ-TMP) combinations in bacterial fish pathogens and their pharmacokinetic properties in po stsmolts of Atlantic salmon Salmo salar (250 +/- 50 g) held in seawate r (10 degrees C) were studied. The bacterial species Aeromonas salmoni cida, Vibrio anguillarum, V. salmonicida, and Yersinia ruckeri were in cluded in the minimum inhibitory concentration (MIG) study. When teste d against a SDZ:TMP concentration of 5:1, V. salmonicida was susceptib le to the lowest (1,000 ng/mL) MIC50 (MIC that inhibits growth of 50% of cultured bacteria), followed by Y. ruckeri and V. anguillarum (1,60 0 ng/mL) and A. salmonicida (3,200 ng/mL). The same order was demonstr ated for a combination of SDZ:TMP at 40:1, but the values were 2-3 tim es higher. The lowest MIC50 of SMX:OMP at 5:1 was demonstrated for V. salmonicida (160 ng/mL), followed by V. anguillarum (400 ng/mL), Y. ru ckeri (1,600 ng/mL), and then A. salmonicida (3,200 ng/mL). Groups of postsmolts were administered one of the following combinations intrave nously or orally: (1) 25 mg SDZ + 5 mg TMP, (2) 25 mg SDZ + 1 mg TMP, or (3) 25 mg SMX + 5 mg OMP. Sulfadimethoxine was absorbed more rapidl y than SDZ although the peak concentration was lower, 4,118 ng/mL vers us 7,920 ng/mL, respectively. The apparent bioavailability for SDZ was calculated to be 46%, the corresponding parameter being 16% for SMX. The bioavailability was 106% (100%) for TMP and was 85% for OMP. These results give reason to question whether the 5:1 ratio between the sul fonamides and the 2,4-diaminopyrimidines, which are currently being us ed in premixes for fish, is optimal.