PHARMACOKINETICS, BIOAVAILABILITY, DISTRIBUTION, AND METABOLISM OF SULFADIMETHOXINE IN THE RAINBOW-TROUT (ONCORHYNCHUS-MYKISS)

Sulfadimethoxine (SDM), a sulfonamide antibacterial drug, was examined in regards to bioavailability, pharmacokinetics, distribution, plasma protein binding, mass balance, and metabolism in the rainbow trout (Oncorhynchus mykiss). Analysis of SDM pharmacokinetics when determined by S-35 counting (parent/metabolite combination) and HPLC (parent) provided estimates for t1/2-alpha, t1/2-beta, V(ss), and Cl(b) of 0.63/0.38 (h), 17.0/15.9 (h), 500.8/421.6 (mL/kg),and 22.7/21.8mL.kg-1.h-1, respectively. Multiple dose administration of[S-35]SDM resulted in a terminal t1/2 of 35.2 h. Sodium SDM (42 and 126 mg/kg) and free drug (42 mg/kg) oral bioavailabilities were 63, 50, and 34%, respectively. Plasma protein binding (15.8 +/- 5.1%) was nonsaturable and nonspecific. Tissues attained the highest levels of SDM equivalents in the bile followed by the intestine, liver, blood, skin, kidney, spleen, gill, muscle, and fat, respectively. Mass balance studies demonstrated a minor role for branchial ((0.6 +/- 0.24%) 25 h) and urinary ((5.46 +/- 2.24%) 24 h) routes of elimination over the first 24 h. SDM and N4-acetylated SDM (N4-A-SDM) were the major constituents for branchial and urinary routes, respectively. Metabolite analysis for select tissues demonstrated a predominance of N4-A-SDM in bile, SDM in plasma, and N4-A-SDM in the liver 20 h after dosing.