A case of deficiency of N-hydroxylation of amobarbital.
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.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000654:Amobarbital / Q000378:metabolism* / Q000652:urine; D001711:Biotransformation; D005260:Female; D006207:Half-Life; D006801:Humans; D006900:Hydroxylation; D007700:Kinetics; D008297:Male; D008661:Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D008875:Middle Aged; D010375:Pedigree; D011247:Pregnancy; D012463:Saliva / Q000378:metabolism; D013997:Time Factors; D014430:Twins, Monozygotic
D000654:Amobarbital