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

1. The disposition of proflavine (PRO) and acriflavine (ACR) were exam ined in channel catfish after intravascular (i.v.) dosing (1 mg/kg) or waterborne exposure(10 mg/l for 4 h). 2. After i.v. dosing, plasma co ncentration-time profiles of parent PRO and ACR were best described by two- and three-compartment pharmacokinetic models respectively. Termi nal elimination half-lives of PRO and ACR in plasma were 8.7 and 11.4h respectively. 3. In animals dosed with C-14-PRO or C-14-ACR, total dr ug equivalent concentrations were highest in the excretory organs and lowest in muscle, fat and plasma. In PRO-dosed animals, residues in th e liver and trunk kidney were composed primarily of glucuronosyl and a cetyl conjugates of PRO; residues in muscle were composed mostly (> 95 %) of the parent drug. In ACR-dosed animals, the parent compound comp rised > 90 % of the total residues in all tissues examined. 4. PRO and ACR were poorly absorbed in catfish during waterborne exposure. At th e end of a 4-h exposure, parent PRO and ACR concentrations in muscle w ere 0.064 and 0.020 mu g/g respectively. Levels in muscle declined bel ow the limit of determination (0.005 mu g/g) within 1-2 weeks.