Pharmacokinetic analysis of plasma concentration and urinary excretion of sulphamonomethoxine and its metabolite in Goettingen minipigs.

The plasma concentration and renal excretion after a bolus intravenous injection of a low (10 mg/kg) or high (100 mg/kg) dose of sulphamonomethoxine (SMM) were studied in five Goettingen minipigs. The time data of plasma concentration after a low dose decreased rapidly and appeared to be linear on semilog graph paper. On the other hand, a decrease in the plasma concentration after a high dose was slow at first, gradually accelerated, then became rapid, showing that SMM disposition after a high dose (100 mg/kg) seemed to be non-linear with capacity-limited elimination. A large amount of the acetyl derivative of SMM (AcSMM), which was determined to be the main excretory product of SMM in urine, was detected in the plasma after SMM injection. As the ratios of the area under plasma concentration-time curve of AcSMM to that of SMM were not significantly different at either dose, the acetylation of SMM may be unsaturable by injection of 100 mg/kg of SMM. Immediately after the injection of a low dose, a rapid hyperbolic increase of the fraction of the cumulative amount of the excretory products in urine was observed. On the other hand, the fraction curve at the high dose rose slowly at first, then rapidly and hyperbolically. These results suggested that the non-linear drug disposition after a high dose (100 mg/kg) of SMM in pigs may be the result of a limited capacity for renal excretion of SMM and excretory products, especially the acetyl derivative.