Maguire J H, Wettrell G, Rane A
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27514.
Br J Clin Pharmacol. 1987 Oct;24(4):554-7. doi: 10.1111/j.1365-2125.1987.tb03212.x.
A 10-year old female on phenytoin therapy developed a rash and lymphadenopathy. H.p.l.c. assays of urinary metabolites indicated no differences in stereoselective metabolism of phenytoin to phenolic and dihydrodiol metabolites as compared with volunteers given the drug or with pediatric patients without adverse reactions. This suggests that no obvious difference in stereoselective metabolism of phenytoin to potentially toxic arene oxides exists between this patient and other patients on phenytoin. Our results are consistent with the hypothesis that differences in peripheral detoxication of phenytoin arene oxides and not differences in hepatic metabolism of phenytoin may be responsible for such adverse reactions.
一名接受苯妥英治疗的10岁女性出现皮疹和淋巴结病。对尿液代谢物的高效液相色谱分析表明,与服用该药物的志愿者或无不良反应的儿科患者相比,苯妥英向酚类和二氢二醇代谢物的立体选择性代谢没有差异。这表明该患者与其他服用苯妥英的患者之间,苯妥英向潜在有毒的芳烃氧化物的立体选择性代谢没有明显差异。我们的结果与以下假设一致,即苯妥英芳烃氧化物外周解毒的差异而非苯妥英肝脏代谢的差异可能是此类不良反应的原因。