Quantitative Studies on Human Urinary Metabolites of Tryptophan as Affected by Isoniazid and Deoxypyridoxine1

Abstract

The influence of iso-niazid and deoxypyridoxine on the urinary excretion of tryptophan metabolites by tuberculous patients was studied. The daily intake of the drugs was increased at weekly intervals until abnormal tryptophan metabolism was observed, following which supplements of thiamine, riboflavin, niacin and pyridoxine were started at weekly intervals to determine their effect on the abnormal metabolism. The subjects all had essentially normal tryptophan metabolism prior to the drug treatment. During the drug treatment the 3-hydroxykynurenine excreted in the urine was adequate to account for 10 to 25% of a 9.8 m[image] (2 g) supplement of L-tryptophan. Kynurenine was often excreted in quantities equivalent to 5 to 10% of the tryptophan administered, while N-a-acetyl-kynurenine and xanthurenic acid were also excreted in abnormally large amounts. The excretion of kynurenic acid was slightly less than normal during isoniazid treatment and abnormally high when deoxypyridoxine was administered. Normal or slightly less than normal amounts of o-aminohippuric acid, anthranilic acid glucuronide, anthranilic acid and N-methyl-2-pyridone-5-carboxamide were found in the urine after ingestion of tryptophan during treatment with either drug. Pyridoxine administration resulted in a return to normal tryptophan metabolism even when the ingestion of isoniazid or deoxypyridoxine was continued. Supplemental thiamine, riboflavin, or niacin had little, if any, effect on the abnormal tryptophan metabolism produced by these drugs.