A case of deficiency of N-hydroxylation of amobarbital

Clinical Pharmacology and Therapeutics
W KalowB K Tang

Abstract

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.

Citations

Sep 1, 1979·European Journal of Clinical Pharmacology·M EichelbaumH J Dengler
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Jan 1, 1982·European Journal of Clinical Pharmacology·B K TangF Y Chan
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Jan 11, 2001·Archives of Pathology & Laboratory Medicine·W Kalow

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