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水杨酸在离体灌注大鼠肾脏中的代谢。水杨尿酸和水杨酸的相互转化。

Metabolism of salicylic acid in the isolated perfused rat kidney. Interconversion of salicyluric and salicyclic acids.

作者信息

Bekersky I, Colburn W A, Fishman L, Kaplan S A

出版信息

Drug Metab Dispos. 1980 Sep-Oct;8(5):319-24.

PMID:6107229
Abstract

Renal metabolism of salicylic acid (SA) to salicyluric acid (SU), as well as the metabolism of SU to SA, was demonstrated in the isolated perfused rat kidney. SU formation was dependent upon the inclusion of a glycine pool and glycine concentration influenced the rate of SU excretion. The total conversion of SA to SU in 1 hr was 7.7% after the administration of 1 mg SA. Administration of increasing amounts of SA diminished this extent of SU formation. The addition of a competitive substrate, benzoic acid, produced a rapid formation and excretion of hippuric acid with a corresponding inhibition of SU formation and excretion. It is important to note that when isolated kidneys were perfused with 2.5 mg SU, 20--30% of the dose was metabolized to SA. Increasing the dose of SU to 10 mg decreased the amount of SA formed. In view of observed reversible SA/SU metabolism, a larger renal contribution to overall salicylate disposition is suggested.

摘要

在离体灌注大鼠肾脏中证实了水杨酸(SA)向水杨尿酸(SU)的肾脏代谢,以及SU向SA的代谢。SU的形成依赖于甘氨酸池的存在,并且甘氨酸浓度影响SU的排泄速率。给予1mg SA后,1小时内SA向SU的总转化率为7.7%。增加SA的给药量会降低SU的形成程度。添加竞争性底物苯甲酸会导致马尿酸的快速形成和排泄,同时相应抑制SU的形成和排泄。需要注意的是,当用2.5mg SU灌注离体肾脏时,20% - 30%的剂量会代谢为SA。将SU的剂量增加到10mg会减少SA的形成量。鉴于观察到的SA/SU可逆代谢,提示肾脏对水杨酸盐总体处置的贡献更大。

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