Rate of Urinary Arsenic Excretion After Giving Acetarsone ("Stovarsol) and "Carbarsone" by Mouth.

Abstract

As part of the necessary pharmacological evaluation of a new drug before it should be tried even in controlled clinical experimentation, its rate of absorption (if given by mouth) and excretion should be studied. If possible this should be done on normal human volunteers in order that any deleterious effects may be noted to be guarded against when used in patients. Especially is this procedure important in order to judge the danger of cumulative effect before venturing to employ arsenical compounds on repeated administration in human therapy. Except for the bare statement that 3-acetylamino-4-hydroxy-phenylarsonic acid (acetarsone N.N.R. or “stovarsol”) is excreted in the urine after oral administration, we have not been able to find any information regarding its absorption or excretion, in spite of the fact that it has considerable toxicity and has been widely exploited in human therapy with some incidence of poisoning. The present-study was undertaken to supply this deficiency in part. Since our laboratory investigation of a considerable number of arsenical compounds revealed several which would seem on experimental evidence to be superior to acetarsone in treating amebiasis, we decided to include in this study the one upon which we had the most satisfactory data. This was 4-carbaminophenylarsonic acid, previously shown on comparison with acetarsone to have a lower toxicity on oral administration, but more amebacidal action in vitro, and with a calculated therapeutic index about 8 times as great. Excretion in the urine is evidence of absorption from the gut following oral administration. The rate of excretion (assuming all the arsenic to be excreted that is absorbed) then would be, for these compounds, an index of the rate of alimentary absorption, and might give some indication of the degree of systemic action to be expected.