Rieder M J, Shear N H, Kanee A, Tang B K, Spielberg S P
Division of Clinical Pharmacology, Hospital for Sick Children, London, Ontario, Canada.
Clin Pharmacol Ther. 1991 Jan;49(1):13-7. doi: 10.1038/clpt.1991.3.
Delayed hypersensitivity reactions are among the most severe adverse effects of the sulfonamides in current clinical use. These reactions appear to occur because of differences in the metabolism and detoxification of reactive metabolites of the sulfonamides. N-Acetylation is a major metabolic pathway for the sulfonamides. Slow acetylation phenotype might be a risk factor for the development of these reactions. We determined the acetylation phenotype of 21 patients who had suffered hypersensitivity reactions to the sulfonamides. There were 11 females and 10 males in the group, with a mean age of 15 years (age range, 1.8 to 50 years). Their acetylator phenotype was determined by determining the ratio of urinary caffeine metabolites (1-methylxanthine to 5-amino-6-formylmethyluracil after an oral dose of 50 mg caffeine). Nineteen (90%) of the patients were slow acetylators compared to a 55% incidence of slow acetylators in a race-matched control population (p less than 0.008). This suggests that a slow acetylator phenotype is a risk factor for the development of sulfonamide hypersensitivity reactions and provides further support for the role of imbalances in genetically determined pathways of metabolism and detoxification of the sulfonamides in the pathogenesis of these reactions.
迟发型超敏反应是当前临床使用的磺胺类药物最严重的不良反应之一。这些反应的发生似乎是由于磺胺类药物活性代谢产物在代谢和解毒方面存在差异。N - 乙酰化是磺胺类药物的主要代谢途径。慢乙酰化表型可能是这些反应发生的一个危险因素。我们测定了21例对磺胺类药物发生超敏反应患者的乙酰化表型。该组中有11名女性和10名男性，平均年龄15岁（年龄范围1.8至50岁）。通过测定口服50毫克咖啡因后尿中咖啡因代谢产物的比例（1 - 甲基黄嘌呤与5 - 氨基 - 6 - 甲酰甲基尿嘧啶）来确定他们的乙酰化表型。与种族匹配的对照人群中55%的慢乙酰化发生率相比，19例（90%）患者为慢乙酰化者（p小于0.008）。这表明慢乙酰化表型是磺胺类药物超敏反应发生的一个危险因素，并进一步支持了磺胺类药物在这些反应发病机制中由基因决定的代谢和解毒途径失衡所起的作用。
