Drayer D E
Am J Med. 1977 Apr;62(4):486-9. doi: 10.1016/0002-9343(77)90402-8.
Drugs that are administered to man may be biotransformed to yield metabolites that are pharmacologically active. These metabolites may accumulate in patients with end-stage renal disease if renal excretion is a major elimination pathway for the metabolite. This is true even if the active metabolite is a minor metabolite of the parent drug as long as the minor metabolite is not further biotransformed but is mainly excreted in the urine. Minor metabolite accumulation may also occur if it is further biotransformed by a pathway that is inhibited in uremia. Some clinical consequences of accumulation of the active drug metabolites of procainamide, meperidine, clofibrate, allopurinol, sulfadiazine and nitrofurantoin in patients with renal failure are discussed. The high incidence of adverse drug reactions seen in renal failure may be explained, in part, by the accumulation of active drug metabolites. Examples of active drug metabolites that do not accumulate in patients with renal failure because of further biotransformations are also included.
给予人体的药物可能会发生生物转化，产生具有药理活性的代谢产物。如果肾脏排泄是该代谢产物的主要消除途径，那么这些代谢产物可能会在终末期肾病患者体内蓄积。即便活性代谢产物是母体药物的次要代谢产物，只要该次要代谢产物不再进行生物转化而是主要经尿液排泄，情况亦是如此。如果次要代谢产物通过一条在尿毒症时受抑制的途径进一步进行生物转化，也可能会发生蓄积。本文讨论了肾衰竭患者体内普鲁卡因胺、哌替啶、氯贝丁酯、别嘌醇、磺胺嘧啶和呋喃妥因的活性药物代谢产物蓄积的一些临床后果。肾衰竭患者中药物不良反应的高发生率部分可能是由活性药物代谢产物的蓄积所致。本文还列举了因进一步生物转化而不会在肾衰竭患者体内蓄积的活性药物代谢产物的例子。
