Biotransformation of Theophylline in Cirrhotic Rats Induced by Carbon Tetrachloride or N,N-Dimethylnitrosamine

흰쥐에서 사염화탄소 또는 N,N-Dimethylnitrosamine에 의한 간경화시 Theophylline의 생체내변환

  • Park, Eun-Jeon (Dept. of Pharmacy, College of Pharmacy, Wonkwang University) ;
  • Kim, Jaebaek (Dept. of Pharmacy, College of Pharmacy, Wonkwang University) ;
  • Sohn, Dong Hwan (Dept. of Pharmacy, College of Pharmacy, Wonkwang University) ;
  • Ko, Geonil (Dept. of Pharmacy, College of Pharmacy, Wonkwang University)
  • 박은전 (원광대학교 약학대학 약학과) ;
  • 김재백 (원광대학교 약학대학 약학과) ;
  • 손동환 (원광대학교 약학대학 약학과) ;
  • 고건일 (원광대학교 약학대학 약학과)
  • Published : 1999.05.01

Abstract

The object of this work was to study the pharmacokinetic differences and the cause of these differences in cirrhotic rats induced by N,N-dimethylnitrosamine or carbon tetrachloride treatment when aminophylline (8 mg/kg as theophylline, i.v.) was injected. The concentrations of theophylline and its major metabolite (1,3-dimethyluric acid) in plasma were determined by HPLC. In addition, formation of 1,3-dimethyluric acid from theophylline in microsomes was determined. In cirrhotic rats, the systemic clearance of theophylline was reduced to $17\%$ of the control value while AUC (area under the plasma concentration-time curve) and $(t_{1/2})_{\beta}$ were increased to about 6 fold and 10 fold, respectively. The formation of 1,3-dimethyluric acid was decreased to $33-41\%$ of the control value in microsomes of cirrhotic rat liver. From these results, it can be concluded that in cirrhotic rats induced by N,N-dimethylnitrosamine or carbon tetrachloride the total body clearance of theophylline is markedly reduced due to a reduced hepatic metabolism.

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