Oates N S, Shah R R, Idle J R, Smith R L
Clin Pharmacol Ther. 1982 Jul;32(1):81-9. doi: 10.1038/clpt.1982.130.
The ability to oxidize a single 50-mg dose of phenformin to its 4-hydroxy metabolite was determined in 195 individuals. Variations in the urinary ratio of phenformin/4-hydroxyphenformin ranged from 1 to 184. Family studies were consistent with the hypothesis that this variability resulted from a single gene mode of inheritance in which impaired hydroxylation of phenformin appears as an autosomal recessive trait. Both genotype frequencies and the degree of dominance of the extensive metabolizer phenotype over the recessive showed a remarkable resemblance to those described for debrisoquine 4-hydroxylation, which was confirmed by the high degree of correlation (rs=0.785, P less than 0.0001) between the phenformin ratio and the debrisoquine metabolic ratio. Such close agreement between the metabolism of these drugs may indicate that the same genetic control is in operation. Such genetic polymorphism of phenformin hydroxylation may have important implications for therapeutic response and for the possibility of toxic effects in a few individuals.
对195名个体测定了氧化单次50毫克苯乙双胍剂量为其4-羟基代谢物的能力。苯乙双胍/4-羟基苯乙双胍的尿排泄率变化范围为1至184。家系研究与以下假设一致：这种变异性是由单基因遗传模式导致的，其中苯乙双胍羟化受损表现为常染色体隐性性状。广泛代谢型的基因型频率及其相对于隐性型的显性程度与描述的异喹胍4-羟化情况显著相似，这通过苯乙双胍比率与异喹胍代谢比率之间的高度相关性（rs = 0.785，P小于0.0001）得到证实。这些药物代谢之间如此紧密的一致性可能表明存在相同的遗传控制。苯乙双胍羟化的这种基因多态性可能对治疗反应以及少数个体出现毒性作用的可能性具有重要意义。
