DISTRIBUTION AND ELIMINATION OF [C-14] SARAFLOXACIN HYDROCHLORIDE FROM TISSUES OF JUVENILE CHANNEL CATFISH (ICTALURUS-PUNCTATUS)

The distribution and loss of radioactivity from tissues were determine d in 60 juvenile channel catfish (Ictalurus punctatus) following oral dosing with the candidate fish therapeutant Sarafin(R) ([C-14] saraflo xacin hydrochloride) at 10 mg/kg for 5 consecutive days. Twelve groups of 5 fish each were sampled at selected times ranging from 3 to 240 h after the last dose was administered, The concentration and content o f sarafloxacin-equivalent activity was determined in liver, gallbladde r, kidney, skin, and skinless fillet by sample oxidation and liquid sc intillation counting; content of sarafloxacin-equivalent activity was determined in stomach and anterior and posterior intestines, Skinless fillet tissues were also analyzed for sarafloxacin and for potential m etabolites by gradient-elution high-performance liquid chromatography (HPLC) with in-line radiometric and fluorescence detection, Loss of ra dioactivity from the whole body conformed to a bimodal elimination pat tern with a rapid initial phase (t(1/2)=11 h) and a slower secondary p hase (t(1/2)=222 h). Tissue and contents of the gastrointestinal tract (i.e. stomach and anterior and posterior intestines) were a principal depot of activity during the first four sample times (3, 6, 12, and 2 4 h); the combined head, skeleton, and fins (i.e. residual carcass) we re the principal depot of activity in samples taken after 24 h. Of tho se tissues sampled 3 h after the last dose, relative sarafloxacin conc entration was greatest in the liver (4.06 mu g equivalents/g) and leas t in the residual carcass (1.13 mu g equivalents/g), Intermediate conc entrations were found in the kidney (2.04 mu g equivalents/g), skinles s fillet (1.71 mu g equivalents/ g), and the skin (1.51 mu g equivalen ts/g). Concentrations of sarafloxacin-equivalent residues in edible sk inless fillet were consistently among the lowest of all tissues examin ed. The highest mean concentration of parent-equivalent material in th e fillet tissue was found 12 h after administration of the last dose ( 2.27 mu g equivalents/g) and declined thereafter, Sarafloxacin constit uted between 80 and 90% of the extractable radioactive residues from t he fillet homogenates. No other peaks were resolved in any of the fill et tissue samples analyzed by HPLC with in-line radiometric detection.