Active drug metabolites and renal failure.
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.
D000107:Acetylation; D001711:Biotransformation; D002994:Clofibrate / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008614:Meperidine / Q000378:metabolism; D008750:Methyldopa / Q000378:metabolism; D009582:Nitrofurantoin / Q000378:metabolism; D010117:Oxypurinol / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011342:Procainamide / Q000378:metabolism; D013449:Sulfonamides / Q000378:metabolism
D004364:Pharmaceutical Preparations; D013449:Sulfonamides; D008750:Methyldopa; D009582:Nitrofurantoin; D008614:Meperidine; D010117:Oxypurinol; D002994:Clofibrate; D011342:Procainamide