PHARMACOKINETICS OF SULPHAMONOMETHOXINE AND SULFADIMETHOXINE FOLLOWING ORAL-ADMINISTRATION TO CULTURED RAINBOW-TROUT (ONCORHYNCHUS-MYKISS)

The pharmacokinetics and metabolites of sulphamonomethoxine (SMM) and sulphadimethoxine (SDM) were studied in rainbow trout after oral administration (300 and 200 mg/kg, respectively) at a water temperature of 15-degrees-C. Both sulphonamide levels were determined by high-performance liquid chromatography. The pharmacokinetics of SMM and SDM were evaluated by a one compartment model with first-order absorption. The absorption and elimination half-lives were 6.9 and 32.6 h for SMM and 5.0 and 24.5 h for SDM. The area under the serum concentration-time curve and mean residence time were 3081 (mug-h/ml) and 70.6 h for SMM and 2127 (mug-h/ml) and 45.8 h for SDM. N4-Acetylsulphamonomethoxine (AcSMM) and N4-acetylsulphadimethoxine (AcSDM) were detected in all tissues, and the concentrations of these metabolites were much higher in the internal organs, especially in bile, than in serum and muscle. The half-lives and elimination time of N4-acetyl metabolites were longer than those of parent sulphonamides. Glucuronide conjugates of SMM and AcSMM were detected in all tissues, and the glucuronide conjugates of SDM and AcSDM were detected in liver, kidney, and bile. Considerable amounts of conjugated AcSMM were observed in bile even at 32 days post-dosing.