Fillastre J P, Baud L, Baumelou A, Blanchard J, Bonvalet J P, Champey Y, Druet P, Glomot R, Imbs J L, Lagier G
J Pharmacol. 1986;17 Suppl 1:41-50.
This is a report of a round table organized during the second meeting of Clinical Pharmacology held in Giens (France) in September 1985. At the beginning of the meeting, the clinical aspects of drug-induced nephrotoxicity were reviewed. Thus we tried to precise the real interest of the studies of proteinuria, urinary cytology, enzymuria and fractional clearances of lithium or magnesium. The most interesting part of our discussions was to know the point of view of men working in drugs companies when a renal abnormality is found during a clinical trial of a drug and when previous experimental studies did not find any renal adverse effects of the drug. It was suggested in a such situation to do particular studies. Methods generally used to study renal physiology as autoradiography micropuncture, microinjection had to be performed to localize the action of the drug along the nephron. It was also discussed of the use of isolated perfused kidney as a tool in drug disposition and the use of renal cells culture. A better understanding of the mechanisms of direct renal toxicity of drugs was obtained from the results of experimental models. It is not so easy, at the present time, to know the mechanisms of immunological drug-induced nephrotoxicity. It seems necessary to develop new experimental models. The results obtained in animals with Cl2Hg or D. Penicillamine or gold salts afford to suspect some mechanisms for these types of nephropathies. This aspect of drug induced nephropathy is more complex because there is a large interindividual variation in susceptibility to these drugs.
这是一篇关于1985年9月在法国吉昂斯举行的临床药理学第二次会议期间组织的一次圆桌会议的报告。会议开始时,回顾了药物性肾毒性的临床方面。因此,我们试图明确蛋白尿、尿细胞学、酶尿以及锂或镁的分数清除率研究的实际意义。我们讨论中最有趣的部分是了解制药公司工作人员在药物临床试验中发现肾脏异常而之前的实验研究未发现该药物有任何肾脏不良反应时的观点。在这种情况下,有人建议进行特殊研究。通常用于研究肾脏生理学的方法,如放射自显影、微穿刺、微注射,必须进行以确定药物沿肾单位的作用部位。还讨论了使用离体灌注肾作为药物处置工具以及肾细胞培养的应用。从实验模型的结果中可以更好地理解药物直接肾毒性的机制。目前,了解免疫性药物性肾毒性的机制并非易事。似乎有必要开发新的实验模型。在动物身上用氯化汞、青霉胺或金盐得到的结果使人怀疑这些类型肾病的某些机制。药物性肾病的这一方面更为复杂,因为个体对这些药物的易感性存在很大差异。