Buters J T, Reichen J
Department of Clinical Pharmacology, University of Berne, Switzerland.
Biochem Pharmacol. 1990 Aug 15;40(4):771-7. doi: 10.1016/0006-2952(90)90314-b.
Antipyrine metabolism depends on at least three isoenzymes of cytochrome P450 forming the main metabolites 3-OH-, 4-OH- and norantipyrine. We investigated to which extent antipyrine clearance and metabolite formation in vivo correlate with metabolite formation by microsomal fractions in vitro. The influence of sex was investigated in two rat strains. Antipyrine clearance in saliva was determined in 10-month-old Sprague-Dawley and Dark Agouti rats of either sex. Antipyrine and its metabolites in urine and microsomes were measured by a new HPLC method after solid phase or liquid extraction. Antipyrine clearance was 46% higher in males than in female rats. This was associated with a 40% higher urinary excretion of 3-OH-antipyrine in the male rats, the other metabolites being excreted to a similar extent. This higher production of 3-OH-antipyrine in vivo was paralleled by a higher intrinsic clearance in vitro while no sex difference in intrinsic clearance for the formation of the other metabolites was seen. The correlation between in vivo and in vitro metabolic clearance for 3-OH-antipyrine was good (r = 0.75) but unconvincing for 4-OH- (r = 0.49) and norantipyrine (r = 0.01). This could be due to further metabolism of 4-OH- and norantipyrine.
安替比林代谢至少依赖于细胞色素P450的三种同工酶，这些同工酶可形成主要代谢产物3-羟基安替比林、4-羟基安替比林和去甲安替比林。我们研究了安替比林在体内的清除率和代谢产物形成与体外微粒体部分代谢产物形成的相关程度。在两种大鼠品系中研究了性别的影响。测定了10月龄雄性和雌性斯普拉格-道利大鼠及深色刺豚鼠唾液中的安替比林清除率。采用新的HPLC方法，在固相或液液萃取后测定尿液和微粒体中的安替比林及其代谢产物。雄性大鼠的安替比林清除率比雌性大鼠高46%。这与雄性大鼠3-羟基安替比林的尿排泄量高40%有关，其他代谢产物的排泄程度相似。体内3-羟基安替比林的这种较高生成量与体外较高的内在清除率相平行，而在其他代谢产物形成的内在清除率方面未观察到性别差异。3-羟基安替比林体内和体外代谢清除率之间的相关性良好（r = 0.75），但4-羟基安替比林（r = 0.49）和去甲安替比林（r = 0.01）的相关性不显著。这可能是由于4-羟基安替比林和去甲安替比林的进一步代谢所致。
