奎尼丁试管内对人和大鼠肝微粒体安替比林代谢的影响

EFFECTS OF QUINIDINE ON ANTIPYRINE MFTABOLIMS IN HUMAN AND RAT LIVER MICROSOMAL FRACTIONS IN VITRO

用HPLC方法研究奎尼丁试管内对人和Wistar大鼠肝微粒体安替比林(AP)的3甲基-羟化酶、4-羟化酶和2-脱甲基酶活性的影响。当奎尼丁浓度≥0.02mmol/L,≥0.10mmol/L和≥0.50mmol/L时,可分别显著抑制人肝微粒体AP4-羟化酶、3甲基-羟化酶和2-脱甲基酶的活性;对大鼠肝微粒体,奎尼丁≥0.02mmol/L时,能显著抑制AP的3甲基-羟化酶和4-羟化酶活性,而≥0.10mmol/L时也可抑制2-脱甲基酶活性。奎尼丁对AP的3甲基-羟化酶、4-羟化酶和2-脱甲基酶活性的IC_(50)在人肝微粒体分别为:0.550,0.107和0.450mmol/L;而在大鼠的肝微粒体则分别为:0.340,0.080和0.500mmol/L。

The effects of quinidine in vitro on the metabolism of an-tipyrine by human and Wistar rat liver microsomes were studied with a highperformance liquid chromatograph for simultaneuosly estimating the threemajor metabolites of antipyrine: 4-hydroxyantipyrine, 3-hydroxymethylan-tipyrine and norantipyrine. The concentrations for quinidine to cause asignifcant reduction of activity of human liver microsome antipyrine 4-hydroxylase. 3 methyl-hydroxylase and 2-demethylase were≥0. 02, 0. 1 and0. 5 mmol/L, respectively. However, in rat liver microsome, quinidine atthe concentration of≥0. 02mmol/L can reduce the activities of both antipy-rine 4-hydroxylase and 3 methyl-hydroxylase, and at or above 0. 1mmol/L,it significantly inhibited the activity of antipyrine 2-demethylase. Theconcentrations of quinidine to cause 50% reduction of the activities (IC_(50))for antipyrine 3 methyl-hydroxylase, 4-hydroxylase and 2-demethylase were0.550, 0. 107 and 0.450 mmol/L in man, and 0. 340, 0.080 and 0.500mmol/Lin rat, respectively.