Disposition kinetics of sulphadiazine in normal and diabetic rabbits

Influence of alloxan induced metabolic disorder on the biodisposition kinetics of a weakly acidic drug sulphadiazine was investigated in rabbits. In 12 rabbits, mean +/- SD blood pH was 7.45 +/- 0.05, plasma glucose 123 +/- 10.6 mg%, plasma total lipids 336 +/- 124 mg% and plasma urea 36 +/- 6 mg%. After treatment with 150 mg/kg alloxan intravenously the blood pH was 7.20 +/- 0.06, plasma glucose 393 +/- 80.3, total lipids 532 +/- 181 and plasma urea was 48 +/- 10 mg%. Disposition kinetics showed that the plasma concentration of sulphadiazine was significantly (P less than 0.01) higher in normal condition when compared with that of metabolically altered. The zero-time plasma concentration was significantly (P less than 0.01) higher, apparent volume of distribution and total body clearance were significantly (P less than 0.01) lower in the normal than in the metabolically altered condition of rabbits. Elimination rate constant and the half-life did not reveal any significant difference in the normal and metabolically altered conditions. These studies demonstrate that the clinical biochemical conditions can influence the disposition kinetics and fate of weakly acid, and possibly of the weakly basic drugs. Therefore, the therapeutic standards of the drugs need be verified in the condition in which the drugs are to be employed clinically.