Bioavailability, disposition and pharmacokinetics of 14C-ormetoprim in rainbow trout (Salmo gairdneri)

1. Uptake, bioavailability, tissue disposition, and elimination of 14C were examined in rainbow trout following intravascular and per os dosing of 14C-ormetoprim (8 mg/kg). 2. Plasma clearance was rapid following a single i.v. dose (t1/2 alpha = 0.54 h, t1/2 beta = 17.5 h) with an apparent volume of distribution (Vss) of 4.85 l/kg. An increase in both t1/2 alpha (0.67 h) and t1/2 beta (36.7 h) was seen following multiple i.v. doses (steady state). 3. Oral dispositional studies revealed the highest concentration of OMP in bile, kidney and liver, indicating significant renal and hepatic extraction. Significant OMP residues were seen in skin (0.90 p.p.m.) and muscle (0.15 p.p.m.) at 38 days. 4. Peak absorption time of orally administered OMP was 12 h with an apparent bioavailability of 87%. 5. Intravascularly administered OMP was 33% and 31% protein-bound at 1 and 6 h respectively, and binding was non-specific and non-saturable by Scatchard analysis.