Methyltestosterone pharmacokinetics and oral bioavailability in rainbow trout (Oncorhynchus mykiss)

14C-methyltestosterone pharmacokinetics after intraarterial (2 and 20 mg/kg) and oral (30 mg/kg) administration were investigated in rainbow trout at 15 degrees C. Plasma concentrations of methyltestosterone were determined by reverse phase high performance liquid chromatography (HPLC) in combination with reverse isotope dilution for up to 6 and 12 days after oral and intraarterial administration, respectively. Methyltestosterone pharmacokinetic parameter values after intraarterial administration were determined using a two compartment model (WinNonlin). For the 2 and 20 mg/kg doses, respectively, the parameter values were, area under the plasma concentration-time curve (11.2 and 82.3 micromol h/l), total body clearance (0.640 and 0.903 l/h per kg), distribution half-life (4.13 and 8.23 h), elimination half-life (54.9 and 58.6 h), volume of the central compartment (3.83 and 13.9 l/kg), volume of distribution at steady state (6.06 and 26.8 l/kg), and the mean residence time (9.57 and 22.7 h). After oral administration, the following parameter values were assessed using a model-independent method, peak concentration (3.03 micromol/l), time of concentration peak (8.80 h), mean absorption time (13.8 h), and area under curve (AUC)(0-->infinity) (90.2 micromol h/l). A two compartment model analysis of the average plasma concentration-time profile after oral administration showed that absorption followed first-order kinetics with a half-life of 4.7 h. The oral bioavailability of methyltestosterone from food was about 70%.