PHARMACOKINETICS, TISSUE DISTRIBUTION, AND METABOLISM OF NITROFURANTOIN IN THE CHANNEL CATFISH (ICTALURUS-PUNCTATUS)

The pharmacokinetics, tissue distribution, and metabolism of the drug nitrofurantoin were examined in the channel catfish (Ictalurus punctat us) after intravascular or oral dosing. Mean plasma concentrations of nitrofurantoin after intravascular administration at 1 and 10 mg kg-1 of body weight were best fit to two- and three-compartment pharmacokin etic models, respectively. Nitrofurantoin was rapidly eliminated from the plasma after intravascular dosing; at 1 and 10 mg kg-1, the termin al half-lives were 23 and 46 min, respectively. After oral dosing at 1 mg kg-1, peak plasma concentrations (0.06 mug ml-1) occurred at 2 h; the bioavailability was 17%. Residues of nitrofurantoin and its metabo lites in the tissues were initially eliminated rapidly but persisted a t the later sampling times. Residue concentrations were highest in the plasma and excretory tissues. Approximately 21% and 4% of the oral do se were eliminated in the urine and bile, respectively. Parent nitrofu rantoin was the major radiolabelled compound found in the urine; howev er, the percentage of total residues composed of metabolites increased with time. Biliary residues consisted mostly of nitrofurantoin metabo lites. High-performance liquid chromatography revealed the presence of at least five metabolites in the urine and bile.