Toxicity and pharmacokinetics of the antibiotic fumagillin in yearling rainbow trout (Salmo gairdneri)

Yearling trout were administered fumagillin dicyclohexylamine (FDCH), an antibiotic that has shown promise for controlling myxozoan parasites in fish. FDCH was fed at 0.25 or 1 g/kg food at 1.5% body weight per day for 60 days, and gill, liver, kidney, spleen, thymus, intestine, and heart were examined histologically. In both treatment groups the hematopoietic tissue of the kidney and spleen was reduced and hematocrit was significantly lower relative to controls. No alteration was found in liver, intestine, heart, thymus, or gill. FDCH was also administered to trout through an indwelling catheter placed in the dorsal aorta. Plasma FDCH was measured using reverse-phase HPLC, and clearance microconstants were estimated. At the highest doses (60 and 30 mg/kg body wt) fumagillin was lethal within about 6 hr, and histological examination revealed extensive toxic alteration in liver and posterior kidney. Plasma clearance at 6 and 3 mg/kg fit a two-compartment model with a rapid α phase (i.e., 20 min) but a prolonged β phase (5.4 days). Although these fish survived for at least 96 hr, renal tubular alteration remained.