大鼠对佐美酸（McN - 2783 - 21 - 98）的肾脏处理情况。

Renal handling of zomepirac sodium (McN-2783-21-98) in the rat.

作者信息

O'Neill P J, Yorgey K A, Migdalof B H, Gussin R Z

出版信息

J Pharmacol Exp Ther. 1979 Jun;209(3):366-70.

Abstract

The plasma and renal clearance of zomepirac, a weak organic acid, was investigated in anesthetized CR Wistar rats after administration of single bolus i.v. injections or continuous i.v. infusions of the 14C-labeled compound. Adjustment of urine pH to the alkaline range caused more than an 8-fold lowering of the plasma elimination half-life (from 7.0 to 0.8 hr) and enhanced renal clearance by a factor of 53 compared to control. Acidification of the urine or probenecid administration increased the elimination half-life (to 10.9 and 17.5 hr, respectively), and decreased renal and plasma clearance of zomepirac. Since zomepirac is highly bound to plasma proteins (approximately 98%), only a small fraction of the drug is available for filtration at the glomerulus. Therefore, the renal elimination of zomepirac is accomplished mainly by active tubular secretion. Passive nonionic reabsorption is a major factor in determining the net clearance of the drug.

摘要

在麻醉的CR Wistar大鼠中，静脉注射单剂量或持续静脉输注14C标记的弱有机酸佐美酸后，研究了其血浆清除率和肾脏清除率。与对照组相比，将尿液pH调节至碱性范围可使血浆消除半衰期降低8倍以上（从7.0小时降至0.8小时），并使肾脏清除率提高53倍。尿液酸化或给予丙磺舒会延长消除半衰期（分别延长至10.9小时和17.5小时），并降低佐美酸的肾脏和血浆清除率。由于佐美酸与血浆蛋白高度结合（约98%），只有一小部分药物可用于肾小球滤过。因此，佐美酸的肾脏消除主要通过肾小管主动分泌完成。被动非离子重吸收是决定药物净清除率的主要因素。