Vermeij P, Ferrari M D, Buruma O J, Veenema H, de Wolff F A
Department of Neurology, University Hospital of Leiden, The Netherlands.
Clin Pharmacol Ther. 1988 Nov;44(5):588-93. doi: 10.1038/clpt.1988.198.
The mode of inheritance of insufficient phenytoin p-hydroxylation was studied in the family of a patient who had previously suffered from a phenytoin intoxication caused by insufficient metabolism of this drug. This family was compared with a control group. The rate of phenytoin metabolism was derived from the phenytoin/metabolite ratio in serum 6 hours after an oral test dose of 300 mg phenytoin. The propositus, a brother and a sister, were very slow metabolizers of phenytoin, with a metabolic ratio of approximately 20. In the other individuals, 22 family members of the second generation and 37 control subjects, a metabolic ratio of 4.7 +/- 2.2 (mean +/- SD; n = 59) was found. When comparing the members of the second generation (F2) with the control group, two statistically significantly different groups appear to exist: F2, with a metabolic ratio of 6.6 +/- 1.7 (mean +/- SD; n = 22), and the control group, with a metabolic ratio of 3.7 +/- 1.8 (mean +/- SD; n = 37) (p less than 0.001). Based on these results the mode of inheritance of this defect seems to be autosomal recessive.
对一名曾因苯妥英代谢不足而发生苯妥英中毒的患者的家族进行了苯妥英p - 羟基化不足的遗传模式研究。将这个家族与一个对照组进行比较。苯妥英代谢率由口服300mg苯妥英测试剂量6小时后血清中苯妥英/代谢物比值得出。先证者、其一个兄弟和一个姐妹是苯妥英的慢代谢者，代谢比值约为20。在其他个体中，第二代的22名家族成员和37名对照受试者的代谢比值为4.7±2.2（均值±标准差；n = 59）。将第二代成员（F2）与对照组比较时，似乎存在两个统计学上有显著差异的组：F2代谢比值为6.6±1.7（均值±标准差；n = 22），对照组代谢比值为3.7±1.8（均值±标准差；n = 37）（p＜0.001）。基于这些结果，这种缺陷的遗传模式似乎是常染色体隐性遗传。
