Pharmacokinetics, Bioavailability, Distribution, and Metabolism of Sulfadimethoxine in the Rainbow Trout (Oncorhynchus mykiss)

Abstract

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 35S counting (parent/metabolite combination) and HPLC (parent) provided estimates for t1/2α, t1/2β, Vss, and Clb, of 0.63/0.38 (h), 17.0/15.9 (h), 500.8/421.6 (mL/kg), and 22.7/21.8 mL∙kg−1∙h−1, respectively. Multiple dose administration of [35S]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.

Pharmacokinetics, bioavailability, plasma protein binding and disposition of nalidixic acid in Rainbow Trout (Oncorhynchus mykiss)

“…Trout administered NA i.v. exhibited a mean total body clearance (Cl,) of 31.5 f 8.0 ml/kg/h) which was considerably higher than that demonstrated in similarly acclimated trout for, oxolinic acid (16.9 ml/kg/h) (Kleinow et al 1992b), sulphadimethoxine (21.8 ml/kg/h) (Kleinow et al 1992a), and ormetoprim Xenobiotica Downloaded from informahealthcare.com by University of Otago on 07/17/15…”

“…I4C-NA protein binding in trout was much lower than the binding reported for NA in mammals (rat, dog, man), which can exceed 90% (Izumi and Kitagawa 1989). Comparatively low protein binding has been demostrated for numerous agents in trout including ormetoprim (33%) (Droy et al 1990, Kleinow andMcElroy 1990), sulphadimethoxine (1 6.6%) (Kleinow et al 1992a), and oxolinic acid (27%) (Bjorklund and Bylund 1991).…”

Sulfadimethoxine in giant freshwater prawns (Macrobrachium rosenbergii): an attempt to estimate the withdrawal time by a population pharmacokinetic approach

“…In the present study, SDM concentrations in the muscle of prawns were first described by a noncompartmental analysis. Studies in lobsters, Homarus americanus (Barron et al ., ; James & Barron, ), catfish, Ictalurus punctatus (Squibb et al ., ), and rainbow trout, Oncorhynchus mykiss (Kleinow & Lech, ; Kleinow et al ., a), have previously demonstrated a two‐compartment model for SDM. The two‐compartmental model was initially attempted from individual data sets, but the residual analysis revealed limitations and prompted the development of a more advanced population analysis.…”

“…The SDM half‐life of elimination for catfish (13 h; Squibb et al ., ) and trout (17 h; Kleinow et al ., ) was similar to that found in the present study for the i.m. and oral gavage routes of administration, whereas the lobster half‐life was significantly longer (77 h).…”

Distribution and depletion of sulfadiazine after a multiple per os dosing in gilthead sea bream (Sparus aurata) fed two different diets

“…Metabolism of sulfonamides under N4-acetylation, hydroxylation and glucuronidation occurs in animals including fish (Grondel et al, 1986;Squibb et al, 1988;Ishida, 1989;van Ginneken et al, 1991;Kleinow et al, 1992;Nouws et al, 1993;Uno et al, 1993;Zheng et al, 1994;Samuelsen et al, 1995Samuelsen et al, , 1997Samuelsen, 2006). N4-acetylation has been reported as the major metabolic route in fish (Squibb et al, 1988;Uno et al, 1993;Samuelsen et al, 1995).…”