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

Abstract

1. Uptake, bioavailability, tissue disposition, and elimination of ¹⁴C were examined in rainbow trout following intravascular and per os dosing of ¹⁴C-ormetoprim (8mg/kg).

2. Plasma clearance was rapid following a single i.v. dose (t_1/2α=0.54 h, t_1/2β=17.5 h) with an apparent volume of distribution (V_ss) of 4.851/kg. An increase in both t_1/2α (0.67 h) and t_1/2β (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 12h with an apparent bioavailability of 87%.

5. Intravascularly administered OMP was 33% and 31% protein-bound at 1 and 6h respectively, and binding was non-specific and non-saturable by Scatchard analysis.