Influence of the genetically controlled deficiency in debrisoquine hydroxylation on antipyrine metabolite formation.
Influence of the genetically controlled deficiency in debrisoquine hydroxylation on antipyrine metabolite formation.
复制标题
遗传控制的异喹啉羟基化缺陷对安替比林代谢物形成的影响。
作者：
M. Danhof;J. Idle;M. Teunissen;T. Sloan;D. Breimer;R. Smith
通过给予14例戊硫喹代谢旺盛者和10例戊硫喹代谢不良者500 mg安替比林，研究了戊硫喹羟基化基因控制不足对安替比林代谢物形成的影响。通过唾液浓度时间曲线测定安替比林的药动学，并测定给药后32h 4-羟安替比林、去甲安替比林、3-羟甲基安替比林、3-羧安替比林的尿累积排泄量。两组的安替比林消除半衰期、分布容积和总清除率几乎相等。除3-羟甲基安替比林外，代谢差组的安替比林代谢差组的安替比林代谢差组的安替比林代谢差组少30% （p < 0.01）。然而，当计算产生这种代谢物的清除率值时，这种差异仅达到临界显著性（p小于0.1）。结果表明，不同种类的药物氧化酶（细胞色素P-450系统）参与了碎屑喹和安替比林的代谢。可能负责羟化碎片喹的酶部分参与了3-羟甲基安替比林的形成。
The influence of the genetically controlled deficiency in debrisoquine hydroxylation on antipyrine metabolite formation was studied by giving 500 mg antipyrine to 14 extensive and 10 poor metabolizers of debrisoquine. The pharmacokinetics of antipyrine were determined on the basis of the saliva concentration time curve and the cumulative urinary excretion of 4-hydroxyantipyrine, norantipyrine, 3-hydroxymethyl-antipyrine, and 3-carboxyantipyrine was measured for 32 h following drug administration. Antipyrine elimination half-life, volume of distribution, and total clearance were almost equal for the two groups. Significant differences in the excretion of antipyrine metabolites were not observed, except for 3-hydroxymethyl-antipyrine which was excreted in poor metabolizers about 30% less than in extensive metabolizers (p less than 0.01). However, this difference only reached borderline significance (p less than 0.1) when clearance values for production of this metabolite were calculated. It is concluded that different species of the drug-oxidizing enzymes (cytochrome P-450 system) are involved in the metabolism of debrisoquine and antipyrine. Possibly the enzyme responsible for hydroxylating debrisoquine is partly involved in the formation of 3-hydroxymethyl-antipyrine.