An In vivo and In vitro Study on Hepatic Microsomal Drug Oxidation in Patients with Various Liver Diseases
スポンサーリンク
概要
- 論文の詳細を見る
Antipyrine has been used as a model drug to investigate the drug metabolism in man. The plasma half-life of antipyrine (<I>in vivo</I> study) and microsomal aniline hydroxylase (<I>in vitro</I> study) were determined in patients with various liver diseases to demonstrate wheather <I>in vivo</I> drug elimination represented <I>in vitro</I> drug metabolism or not.<BR>One of the metabolites of antipyrine, 3-hydroxymethy1-2-methy1-1-phenyl-3-pyrazolin-5-one (AN-CH<SUB>2</SUB>OH), gave 6 per cent absorbance that of antipyrine under the same colorimetric procedure of antipyrine determination. However, using GLC method, AN-CH<SUB>2</SUB>OH was not detected in the extract of serum drawn from a subject given antipyrine orally. Amount of unchanged antipyrine excreted in the urine was only 3 to 5 per cent in 24 hours and the longer the half-life was, the more unchanged antipyrine was excreted. Therefore, it was evident that elimination of antipyrine from plasma indicated velocity of antipyrine metabolism.<BR>After observing a close correlation between aniline hydroxylase and antipyrine hydroxylase activities in rat liver microsome, aniline hydroxylase activity was used as an indicator of in vitro drug metabolism in man.<BR>The values of plasma half-life of antipyrine and the values of microsomal aniline hydroxylase activity in patients with acute hepatitis (convalescent stage), and chronic hepatitis (active form) were widely distributed, but did not significantly differed from those of normal controls. On the other hand, the drug metabolizing activity in patients with liver cirrhosis was markedly decreased both in <I>in vivo</I> and <I>in vitro</I> studies.<BR>The velocity of antipyrine metabolism and the microsomal aniline hydroxylase activity was proved to be well correlated (r=0.79) in subjects in which <I>in vitro</I> and <I>in vivo</I> study were carried out simultaneously.<BR> From the results obtained above it was concluded that the elimination of antipyrine from plasma reflects hepatic microsomal drug metabolism.
- Japan Society of Clinical Chemistryの論文