Urinary Excretion of Hydrazine Derivatives of Isonicotinic Acid in Normal Humans

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Abstract
Urinary excretions after oral doses to normal humans of 2 anti-tubercular compounds, isonicotinic acid hydrazide (Rimifon) and 1-isonicotinyl-2-isopropyl hydrazine (Marsilid), have been studied by means of the colorimetric reaction with 10% cyanogen bromide in ammonia buffer. Direct assays were taken as a measure of free isonicotinic acid and the increases on permanganate treatment attributed to Rimifon or Marsilid, pending positive identification of the excretion products. The influence of non-specific chromogens was eliminated almost entirely by parallel assays of pre-dosage urines. Total excretions of isonicotinic acid plus unhydrolyzed drug in 24 hrs. average 54 and 60% of the dose of Marsilid and Rimifon, respectively; after 48 hr., the avg. excretion in both cases totals 65%. Excretion of Rimifon is more rapid than that of Marsilid in the first 8 hrs. after dose. Approx. half of the 24 hr. excretion after Rimifon is in the unhydrolyzed form, but unhydrolyzed Marsilid accounts for only 1/4 of the total excretion. The greater excretion of the split product after Marsilid results apparently from the longer retention of this drug in the body.