Potentiated Sulfonamides: In Vitro Inhibitory Effect and Pharmacokinetic Properties in Atlantic Salmon in Seawater

Abstract

The in vitro antibacterial activities of one sulfadimethoxine-ormetoprim (SMX–OMP) and two sulfadiazine-trimethoprim (SDZ–TMP) combinations in bacterial fish pathogens and their pharmacokinetic properties in postsmolts of Atlantic salmon Salmo salar (250 ± 50 g) held in seawater (10°C) were studied. The bacterial species Aeromonas salmonicida, Vibrio anguillarum, V. salmonicida, and Yersinia ruckeri were included in the minimum inhibitory concentration (MIC) study. When tested against a SDZ : TMP concentration of 5:1, V. salmonicida was susceptible to the lowest (1,000 ng/mL) MIC50 (MIC that inhibits growth of 50% of cultured bacteria), followed by Y. ruckeri and V. anguillarum (1,600 ng/mL) and A. salmonicida (3,200 ng/mL). The same order was demonstrated for a combination of SDZ : TMP at 40: I, but the values were 2–3 times 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. ruckeri (1,600 ng/mL), and then A. salmonicida (3,200 ng/mL). Groups of postsmolts were administered one of the following combinations intravenously 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 rapidly than SDZ although the peak concentration was lower, 4,118 ng/mL versus 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 sulfonamides and the 2,4-diaminopyrimidines, which are currently being used in premixes for fish, is optimal.