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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Oral bioavailability and disposition of sulphadimethoxine in lobster, Homarus americanus, following single and multiple dosing regimens.

1. Single and multiple oral doses of sulphadimethoxine or sodium sulphadimethoxine were administered by gavage to lobster, and sequential samples of haemolymph were taken for analysis of parent sulphadimethoxine. Single doses of sodium sulphadimethoxine were given over a dose range of 14-70 mg/kg. Five 42-mg/kg doses of sulphadimethoxine on alternate days were administered for the multiple-dose studies. Some experiments were conducted with radiolabelled (35S or 14C) sulphadimethoxine, and the tissue distribution of radioactivity was determined at different killing times. 2. Pharmacokinetic parameters were obtained by fitting sulphadimethoxine concentrations in haemolymph to a one-compartment model. Oral bioavailability at the 42-mg/kg dose, calculated from the area under the haemolymph concentration-time curve (AUC) relative to the AUC from intravascular administration, was between 47 and 52% for single or multiple doses of the free drug. The bioavailability of sodium sulphadimethoxine was dose dependent, at 97% for the 14 mg/kg dose, and 25% for the 70-mg/kg dose. The low bioavailability at the high dose probably resulted from poor absorption due to the limited solubility of sulphadimethoxine at the low pH of the lobster gastrointestinal tract. 3. Sulphadimethoxine and several polar metabolites were excreted in lobster urine. Polar metabolites were also found in the hepatopancreas and haemolymph. At least 20% of the 42-mg/kg dose was metabolized. The major vertebrate metabolite of sulphadimethoxine, N-acetylsulphadimethoxine, was a very minor metabolite in lobster. The identities of the polar metabolites were not established. 4. Elimination of sulphadimethoxine residues from muscle to < 0.1 microgram sulphadimethoxine equivalent/g tissue required 40 days after a single dose, or 44 days after the last of multiple doses. Concentrations of sulphadimethoxine residues in all other tissues were always greater than muscle concentrations. Data showed that sulphadimethoxine residues were very persistent in lobster tissues.[1]

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