Abstract
Summary
Urinary excretions after oral dosage of Rimifon and Marsilid to 9 normal humans have been studied colorimetrically by means of the reaction with 10% cyanogen bromide in ammonia buffer. The influence of non-specific chromogens has been eliminated to a large degree by parallel, assays of pre-dosage control urines. The concentration of metabolite in which the hydrazide linkage has been split was determined by direct assay and the results expressed as “free isonicotinic acid” pending positive identification. The increase in colorimetric readings upon permanganate treatment has been ascribed to unchanged Rimifon or Marsilid, although, again, the exact nature of these excretion products has not been ascertained. Total excretions in 48 hours average about 65% of the dose of both Rimifon and Marsilid, but in the same period the excretion of unhydrolyzed Marsilid is only about half that of Rimifon. In the first few hours after dose, the relative rate of excretion of Marsilid is still lower, averaging only about one-fourth that of Rimifon. Approximately half of the Rimifon is split prior to excretion and almost identical excretion patterns are found at the 192 and 125 mg dose levels. In case of Marsilid, the excretion of free isonicotinic acid parallels closely its excretion after Rimifon for 8 hours, but the 24- and 48-hour totals of free isonicotinic acid are about 50% higher after Marsilid. This increased excretion of the split product results apparently from the longer retention of Marsilid in the body.
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