Inheritance of poor phenytoin parahydroxylation capacity in a Dutch family

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 (F 2 ) with the control group, two statistically significantly different groups appear to exist: F 2 , 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 < 0.001). Based on these results the mode of inheritance of this defect seems to be autosomal recessive. Clinical Pharmacology and Therapeutics (1988) 44, 588–593; doi: 10.1038/clpt.1988.198