Disposition kinetics and urinary excretion of sulphadimidine in normal and alloxan diabetic dogs.

Disposition kinetics and urinary excretion of sulphadimidine were investigated in 16 dogs following a single intravenous injection (100 mg/kg body weight). Biochemical parameters including blood pH, blood glucose, plasma triglycerides and total plasma proteins of these animals were determined. The animals were injected alloxan (125 mg/kg) intravenously and when blood glucose level exceeded 300 mg%, the biochemical parameters, disposition kinetics and urinary excretion of sulphadimidine were determined again. After alloxan treatment of the dogs, there was a highly significant (P less than 0.01) decrease in blood pH, increase in blood glucose and plasma triglycerides levels when compared with the pretreatment values. The alloxan diabetic dogs showed a highly significant (P less than 0.01) reduction in elimination half-life (t1/2 beta) and apparent volume of distribution (Vd(area)) and increase in overall elimination rate constant (kel), total body clearance (ClB) and percentage of sulphadimidine dose excreted in urine. In normal dogs, one-half of the intravenous dose and after alloxan treatment two-third of the dose was eliminated through urinary excretion during 48 hours after injection. This study shows that the metabolic alterations of alloxan induced diabetes in dogs, influence the drug disposition and urinary excretion which indicate the need for the adjustment of dosage regimen in such metabolic disorders.