Ritchie J C, Crothers M J, Shah R R, Idle J R, Smith R L
Xenobiotica. 1986 May;16(5):503-9. doi: 10.3109/00498258609050255.
The regioselectivity of the metabolic hydroxylation of debrisoquine has been determined in 43 healthy British white volunteers and the priority was found to be in the order 4 greater than 7 greater than 6 greater than 5 greater than 8. The order of preference for hydroxylation position was independent of debrisoquine 4-hydroxylation phenotype. The extent of total aromatic hydroxylation varied widely between individuals and was largely independent of the extent of 4-hydroxylation, and thus of the influence of the DH/DL locus. Two sisters and their blood relations all excreted comparatively large amounts of the phenolic metabolites in their urine, indicating some genetic basis for the control of aromatic oxidation of debrisoquine in man. These same two sisters had previously developed agranulocytosis in association with carbimazole therapy.
在43名健康的英国白人志愿者中测定了去甲丙咪嗪代谢性羟基化的区域选择性，发现其优先顺序为4＞7＞6＞5＞8。羟基化位置的优先顺序与去甲丙咪嗪4-羟基化表型无关。个体间总的芳香族羟基化程度差异很大，且在很大程度上与4-羟基化程度无关，因此也与DH/DL位点的影响无关。两名姐妹及其血亲的尿液中均排出了相对大量的酚类代谢物，这表明人类体内去甲丙咪嗪芳香族氧化的控制存在某种遗传基础。这两名姐妹此前在接受卡比马唑治疗时曾发生粒细胞缺乏症。
