METABOLISM OF C14-ISONIAZID IN HUMANS

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Abstract
The metabolism of isoniazid was studied in tuberculous and nontuberculous patients following intramuscular administration of C14-isoniazid and was reinvestigated following daily oral administration of either pyridoxine or PAS for 3 to 4 weeks. Plasma concentrations of C14 -activity are linear with a dose at therapeutic dose levels. One hour after drug administration C14-activity in the cerebrospinal fluid is approximately one-fifth the activity in plasma. Seventy-five to 95% of the injected radio-activity was excreted in 24 hours. Chromatographic separation of urinary isoniazid metabolites demonstrated at least 3 major bands, 2 of which were positively identified as acetyl isoniazid and iso-nicotinic acid. Acetyl isoniazid excretion in different subjects varied from 25 to 70%, and isonicotinic acid excretion varied from 20 to 40%. These 2 urinary metabolites comprised from 50 to 95% of the injected C14-isoniazid activity. Neither pyridoxine nor PAS influenced appreciably Cl4-activity plasma turnover time or urinary excretion rates. No significant change in urine content of acetyl isoniazid or isonicotinic acid could be induced by the addition of either pyridoxine or PAS to the treatment regimen.