Pharmacokinetic profile and tissue distribution of sulfamethazine in pigs and rats

돼지와 랫트에서 sulfamethazine의 약물동태학 및 조직분포

  • Received : 1996.08.17
  • Published : 1997.06.25

Abstract

In order to establish optimal dosage schedules and withdrawal times for sulfamethazine(SMZ) in pigs, pharmacokinetic and tissue distribution experiments were conducted in pigs. For comparative purposes, tissue depletion kinetics are also studied in rats. From three pigs administered with SMZ i.v., the pharmacokinetic profile of SMZ in two pigs was adequately described by a one-compartment open model whereas that in one pig was patterned after a two-compartment open model. Volume of distribution(Vd) was 0.48~0.57 L/kg and biological half-life($t_{1/2}$) was 11.8-16.8 h. From three pigs dosed with SMZ p.o., pharmacokinetic profile was explainable with a one-compartment open model. Time to reach maximum SMZ concentration in serum (Tmax) was 2.8 h, 3.2 h and 7.5 h. Elimination half-life was 2.8-7.5 h. The descending order in concentration of SMZ was plsama > kidney > liver > lung > heart > pancreas > spleen > duodenum > ileum > brain > adipsoe tissue from three pigs sacrificed at 5h, 29h and 54h after the administration of SMZ, p.o.. The protein binding of SMZ in pigs was 55.2%($2.5{\mu}g/ml$), 71.5% ($5{\mu}g/kg$) and 71.5%($10{\mu}g/ml$). The mean systemic bioavailability (F) of SMZ p.o. was 49.1 %. Meanwhile the pharmacokinetic profile of SMZ in rats was adequately described by a one-compartment open model. Absorption of SMZ p.o. in the rat was very rapid. In conclusion, the oral optimal dosage regimen of SMZ for pigs was the initial dose of 45.7 mg/kg followed by the maintenance dose of 30.2 mg/kg for high specific pathogens to SMZ. The time to reach below the stipulated residual allowable concentration (0.1 ppm) was calculated 93 h after oral administration of 200 mg/kg recommended by manufactureres.