Possibility of saturation in renal excretion after high dose of intravenous sulfamonomethoxine in pigs.

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Abstract
The plasma kinetics and the renal excretion after 3 intravenous doses (10, 50 and 100 mg/kg) of sulfamonomethoxine (SMM) were studied in 10 commercial pigs (3.5-6 months old) and the possible causal factor of nonlinear plasma kinetics after high doses of SMM was examined. A considerable amount of acetylated metabolite of SMM (AcSMM) appeared in Plasma after any of 3 doses examined. About 80% of excretory products in urine was identified as AcSMM. These results imply that a main route of the drug elimination is acetylation followed by renal excretion. The corrected values of AUC, which were obtained by dividing the area under the plasma concentration versus time curves of SMM or AcSMM by the ratio of the examined dose (10, 50 or 100 mg/kg) to the lowest dose (10 mg/kg), increased dose-dependently. No significant difference in the ratio of AUC of AcSMM to that of total (SMM+AcSMM) was found among the doses. These results suggest that the synthetic reaction of AcSMM may not be saturable by injection of the higher doses. The renal clearances of SMM and AcSMM after the 10 mg/kg dose were nearly constant throughout the experiment, whereas those after the higher doses were low at the early stage and became high thereafter. Consequently, the saturation in renal excretion at the early stage of the elimination after the higher doses (50 and 100 mg/kg) may be a possible causal factor of the nonlinear kinetics of SMM.