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Journal of Pharmacology And Experimental Therapeutics, Vol. 150, Issue 2, 298-304, 1965
Copyright © 1965 by American Society for Pharmacology and Experimental Therapeutics

STUDIES ON THE METABOLIC BASIS FOR THE GENETICALLY DETERMINED CAPACITIES FOR ISONIAZID INACTIVATION IN MAN

J. H. Peters 1, K. S. Miller 1, and P. Brown 1

1 The Christ Hospital Institute of Medical Research, Cincinnati, Ohio, and The National Center for Primate Biology, University of California, Davis, California

The metabolism of isoniazid, acetylisoniazid and isonicotinic acid has been studied after oral administration in volunteers by measuring the urinary excretion of parent compounds and metabolites. The relatively small group of experimental subjects was easily separated into "rapid" and " slow" inactivators of isoniazid on the basis of the excretion of the parent hydrazide after administration of either 5 or 10 mg isoniazid/kg. At either dose, the primary metabolic reaction determining inactivator status was shown to be acetylation. At the higher dose, it was observed that the isonicotinyl hydrazones fraction of metabolites consisted principally of pyruvic acid and agr- ketoglutaric acid hydrazones. All subjects showed essentially the same ability to excrete and metabolize orally administered acetylisoniazid; no isoniazid or isoniazid hydrazones were detected. Analyses for hydrazine or acetylated hydrazine showed that only insignificant amounts of these compounds were excreted by subjects receiving either isoniazid or acetylisoniazid. After administration of isonicotinic acid, the subjects excreted the parent acid and its glycine conjugate in amounts that varied among the individuals, but the sum of the two excretory products accounted for very nearly the total dose given. These two compounds were also found after isoniazid and acetylisoniazid administrations. Other derivatives of isonicotinic acid were not detected in any experiment. No correlation between capacities of individuals to acetylate isoniazid and to conjugate isonicotinic acid with glycine could be discerned in these experiments.

Accepted on June 17, 1965




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Copyright © 1965 by the American Society for Pharmacology and Experimental Therapeutics.