Exploratory bioavailability and pharmacokinetic studies of sulphadimethoxine and ormetoprim in the penaeid shrimp, Penaeus vannamei

The pharmacokinetics and bioavailability of sulphadimethoxine (SDM) and ormetoprim (OMP) were examined, following simultaneous administration in penaeid shrimp. The hemolymph concentration versus time data following intra-sinus injection for both SDM (42 mg/kg) and OMP (8.6 mg/kg) were well described by a multiexponential equation suggesting multicompartmental behavior. The SDM:OMP parameter estimates of systemic clearance, steady-state volume of distribution, and disposition half-life were 215:1765 ml/kg · h, 1319:34 382 ml/kg, and 9.0:17.8 h, respectively. Hemolymph protein binding of SDM and OMP was 5.2% and 12.1%, respectively. The bioavailabilities of SDM and OMP were 30% and 32%, respectively. Peak hemolymph concentration (C_max) and time of occurrence of that value (T_max) for SDM following a single oral dose (210 mg/kg) were 25.0 μg/ ml at 4 h, while the corresponding values for OMP were (dose, 42 mg/kg) 0.70 μg/ml at 4 h. The percent of the available oral dose 2 h post-administration for SDM:OMP in the hemolymph, muscle, and hepatopancreas were 5.0:0.6%, 7.8:3.4%, and 2.4:24.8%, respectively. Hemolymph and muscle tissue concentrations were below detectable limits after 48 h for SDM and 24 h for OMP. The SDM:OMP drug combination has good potential as a shrimp chemotherapeutant in that they were rapidly and moderately absorbed, have relatively short half-lives and low hemolymph protein binding which translates to the bulk of absorbed drugs being available for a therapeutic response.