SALVARSAN AND NEOSALVARSAN IN TREATMENT OF SYPHILIS 855 



In experimental syphilis of rabbits the minimal dose necessary to 

 produce a complete cure was found to be between 0.01 and 0.015 gram 

 per kilogram. The tolerated dose by intravenous injection is 0.1 gram. 

 The curative dose of salvarsan in syphilis of rabbits is, therefore, only 

 from one-seventh to one-tenth of the tolerated dose. 



Studies in the Toxicity of Salvarsan. During the past two years 

 Dr. Schamberg, Dr. Raiziss, and I 1 have studied the toxicity of salvarsan 

 and have reached the following conclusions: 



1. Salvarsan may be used in concentrated solutions up to 0.6 gm. 

 in 20 c.c. per 70 kilograms of body weight in animals without any evi- 

 dent increase of toxicity; in man, however, it would appear that the 

 administration of concentrated solutions of salvarsan increases the 

 toxic effects. 



2. The failure to neutralize solutions of salvarsan with alkali leads 

 to an increase in toxicity of 50 to 60 per cent, in solutions of J to 1 per 

 cent, concentration. 



3. The addition of a moderate excess of alkali beyond the amount 

 required for neutralization does not increase the toxicity, as determinable 

 by tlie duration of life of the experimental animal. It is possible, how- 

 ever, that it may have other untoward effects. 



4. The use of sterile fresh distilled water appears to possess advan- 

 tages over sterile stale distilled or non-distilled water as regards toxicity, 

 although the difference in our experiments was not pronounced. 



5. Salvarsan in alkaline solution tends to undergo oxidation on 

 standing, with consequent incresed toxicity, but this substance and its 

 congeners vary considerably in the rapidity of oxidation and in the degree 

 of associated toxicity. The drug should be used reasonably promptly 

 after preparation. If two or three hours' delay is unavoidable, the 

 solution should be kept in a cylinder full to the stopper, so that no air 

 is present. 



6. Several different types of reactive symptoms may occur after 

 the use of salvarsan: (a) immediate, (6) early, and (c) delayed. The 

 immediate symptoms are due to a paresis of the blood-vessels; the early 

 symptoms coming on a few hours after the injection are febrile and 

 gastro-intestinal, and the delayed symptoms may be referable to the 

 brain or the liver and gastro-intestinal tract. This subject is discussed 

 in greater detail on page 867. 



7. Salvarsan and its congeners are not compounds of absolute 

 chemical purity. We cannot, therefore, expect absolute constancy in 

 biologic effects. 



1 Jour. Cut. Dis. Incl. Syphilis, April, 1917. 



