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KMID : 0941819990090010055
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Korean Journal of Clinical Pharmacy
1999 Volume.9 No. 1 p.55 ~ p.61
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Biotransformation of Theophylline in Cirrhotic Rats Induced by Carbon Tetrachloride or N,N-Dimethylnitrosamine
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Abstract
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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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