Diener U, Tuczek H V, Fischer C, Maier K, Klotz U
Naunyn Schmiedebergs Arch Pharmacol. 1984 Jun;326(3):278-82. doi: 10.1007/BF00505331.
In rat experiments and a clinical trial we have examined the suspected nephrotoxic potential of 5-aminosalicylic acid (5-ASA), the biological active metabolite of sulfasalazine (SZ). Male Wistar rats were treated orally for 4 weeks daily with 30 and 200 mg 5-ASA/kg and 75 and 500 mg SZ/kg. The two renal marker enzymes N-acetyl-beta-D-glucosaminidase (NAG; EC 3.2.1.30), alanineaminopeptidase (AAP; EC 3.4.11.2) and creatinine were monitored in urine. At the end of the experiment rats were sacrificed, the removed kidneys histologically examined and drugs, their metabolites and creatinine measured in plasma and urine. In 9 patients treated chronically for their Crohn's disease with 3 X 0.5 g 5-ASA daily in form of suppositories and an oral preparation urinary excretions of NAG, AAP and serum creatinine were also monitored before and during therapy. Neither the animal experiments nor the observations in patients gave any evidence of nephrotoxic lesions induced by 5-ASA. Thus, our data show that in the doses applied, 5-ASA was devoid of altering renal excretion in rats and man.
在大鼠实验和一项临床试验中，我们研究了柳氮磺胺吡啶（SZ）的生物活性代谢产物5-氨基水杨酸（5-ASA）潜在的肾毒性。雄性Wistar大鼠每天口服30和200 mg 5-ASA/kg以及75和500 mg SZ/kg，持续4周。监测尿液中的两种肾脏标记酶N-乙酰-β-D-氨基葡萄糖苷酶（NAG；EC 3.2.1.30）、丙氨酸氨基肽酶（AAP；EC 3.4.11.2）以及肌酐。实验结束时处死大鼠，取出肾脏进行组织学检查，并测定血浆和尿液中的药物、其代谢产物以及肌酐。9例因克罗恩病长期接受治疗的患者，每天使用3次0.5 g栓剂形式和口服制剂形式的5-ASA，在治疗前和治疗期间也监测了NAG、AAP的尿排泄量以及血清肌酐。动物实验和患者观察均未提供任何5-ASA诱导肾毒性损伤的证据。因此，我们的数据表明，在所应用的剂量下，5-ASA不会改变大鼠和人类的肾脏排泄。
