Kalow W, Kadar D, Inaba T, Tang B K
Clin Pharmacol Ther. 1977 May;21(5):530-5. doi: 10.1002/cpt1977215530.
It has been shown recently that the overall metabolism of amobarbital in man is essentially under genetic control. The drug normally undergoes two hydroxylation reactions, leading to 3'-hydroxyamobarbital (C-OH) and N-hydroxyamobarbital (N-OH). This paper describes a sibship in which two mothers who are identical twins show a gross deficiency on N-OH elimination in urine. The whole set of sibship data suggests that this deficiency represents a recessive trait controlled by a single pair of allelic autosomal genes which regulate N-OH formation. Several methodical approaches to assess an individual's capacity for N-OH formation are illustrated. There was no evidence of compensatory or concordant regulation of the two hydroxylation reactions. The case of this family illustrates that the functional lack of a biotransformation reaction is almost certain to be overlooked if one measures only the disappearance of a multimetabolized drug and not the appearance of metabolites.
最近研究表明，人对异戊巴比妥的整体代谢基本上受基因控制。该药物通常会经历两个羟基化反应，生成3'-羟基异戊巴比妥（C-OH）和N-羟基异戊巴比妥（N-OH）。本文描述了一个家系，其中两位同卵双胞胎母亲在尿液中N-OH的消除方面存在严重缺陷。整个家系数据表明，这种缺陷代表一种隐性性状，由一对调节N-OH形成的常染色体等位基因控制。文中举例说明了几种评估个体N-OH形成能力的方法。没有证据表明这两个羟基化反应存在代偿性或协调性调节。这个家庭的案例表明，如果只测量多代谢药物的消失情况而不测量代谢物的出现情况，几乎肯定会忽略生物转化反应的功能性缺失。
