氨基糖苷类药物血清浓度与肾毒性之间的分离现象。

The dissociation between aminoglycoside serum concentrations and nephrotoxicity.

作者信息

Koren G, Klein J, MacLeod S M

机构信息

Dept. of Pediatrics and Pharmacology, University of Toronto.

出版信息

Life Sci. 1988;43(22):1817-23. doi: 10.1016/0024-3205(88)90281-0.

DOI:10.1016/0024-3205(88)90281-0

PMID:3059121

Abstract

Using newborn and adult rats we tested the correlation between aminoglycoside dose, resultant serum and renal cortical concentrations and nephrotoxicity evidenced by creatinine in serum and urine, N-acetylglucosaminidase and beta 2 microglobulins in urine and sphingomyelinase in renal cortical tissue. Our data reveal that aminoglycoside nephrotoxicity is clearly more evident in adult rats despite significantly lower drug serum concentrations and in the presence of substantially higher renal cortical concentrations. These data indicate that high aminoglycoside serum concentrations are not causing nephrotoxicity but rather reflect secondary body accumulation of the drug associated renal damage.

摘要

我们使用新生大鼠和成年大鼠，测试了氨基糖苷类药物剂量、血清及肾皮质浓度之间的相关性，以及血清和尿液中的肌酐、尿液中的N-乙酰氨基葡萄糖苷酶和β2微球蛋白、肾皮质组织中的鞘磷脂酶所证实的肾毒性。我们的数据显示，尽管成年大鼠的药物血清浓度显著较低且肾皮质浓度显著较高，但氨基糖苷类药物的肾毒性在成年大鼠中明显更显著。这些数据表明，高氨基糖苷类血清浓度并非导致肾毒性的原因，而是反映了药物相关肾损伤的继发性体内蓄积。