Metabolic and pharmacokinetic profiles of sulfamethazine in the rat

Rat에서 설파메타진의 대사 및 약물동태학

We used rats as the experimental animal for the elucidation of metabolic patterns and pharmacokinetic profiles of SMZ in the rat, by use of the urine and plasma from predetermined intervals, respectively. Information herefrom would give some insight into species differences and sex differences in the metabolism and pharamcokinetics of drugs, at least SMZ in particular. Results would be summarized as follows: 1. There were two hydorxy metabolites(5-hydroxysulfamethazine and 6-hydroxyethylsulfamethazine) and an acetyl derivative($N_4$-acetyl sulfamethazine) in the 24h-collected urine, on confirmation with each standard materials. There were also two unknown metabolites therein. 2. In the viewpoint of quantitative aspect, $N_4$-acetylsulfamethazine was the largest, hence it is assumed that the acetyl pathway is the major one in the metabolism of SMZ in the rat. 3. As regards sex difference in the rat, the male had more metabolic capacity than the female in metabolism of SMZ. 4. The concenteration-time curves of sulfamethazine(20mg/kg, po) in the plasma compartment were fitted to a one-compartment open model by use of a computer program(NONLIN). 5. There were significant differences(P<0.05) in the pharmacokinetics of sulfamethazine between two sexes in the rat, with higher disposition rate in the male. 6. The emergence of $N_4AcSMZ$ metabolized from SMZ was fast in the plasma of the rat. Half-life of $N_4AcSMZ$ was also. significantly different(P<0.05) between two sexes, suggesting differences in the eliminatory capacity of $N_4AcSMZ$.