Disposition kinetics of trimethoprim in rainbow trout (Oncorhynchus mykiss)

1. The pharmacokinetics of trimethoprim (TMP) following intra-aortic administration were investigated in rainbow trout. 2. The disposition kinetics for TMP were best described by a three-compartment open model. The disappearance of TMP from fish blood was characterized by rapid and pronounced distribution phases and a slow terminal elimination phase. 3. In contrast with pharmacokinetic data of TMP in mammals, the present study documented a long terminal elimination t1/2(36.1 h), large Vdss(5980 ml/kg) and small Clb(2.4 ml/min/kg) for TMP in rainbow trout, thus illustrating the slow biotransformation and elimination capacity, particularly the strong 'holding' capacity (storage) for the drug in trout. 4. The pharmacokinetic profiles in the present study indicated no dose dependency of TMP following three different bolus doses (5, 10 and 50 mg/kg). Hence, the first-order kinetic assumption was verified. 5. Urinary excretion of TMP was a minor elimination route in trout (14.4% dose).