11 
mixtures is largely a matter of conjecture. Herczel® in 1887 carried 
out some experiments upon dogs and was able to show that the exhi- 
bition of acetanilide definitely decreased the alkalinity of the blood. 
Although all methods for determining the alkalinity of the blood 
are unreliable this fact would afl’ord an experimental basis for their 
presence, but the small amount present in the usual t^’pe of acetan- 
ilide mixture would probably be insufficient to make the blood 
materially less acid. 
In this comiection it is important to remember that acetanilide 
causes the formation of methsemaglobin in the blood and that this 
may be hastened by a decrease in the alkalinity of the blood has been 
pointed out by Kobert^ who states that the alkahes prevent the break- 
ing up of the blood cells and the formation of methsemaglobin. The 
exhibition of alkalies, according to Kobert, also serves to aid the 
regeneration of the oxyhsemaglobin, an alkali-methaemaglobin being 
formed as an intermediary product winch changes the blood from 
a chocolate bro\vn to a red and from tins oxyh^emaglobin is formed. 
Another reason for the combination of alkahes vdth acetanilide 
has to do with increasing the solubihty of the drug, the idea formerly 
prevailing that acetanilide was made more soluble and hence more 
easily absorbed when thus prescribed. In 1891 Hall^ gave as a 
reason for the greater activity that had been claimed for antikamnia 
its finely divided state and the presence of sodium bicarbonate, 
which he said made it more soluble. The idea of greater solubihty 
when given with alkahes seems to have been held as late as 1906 for 
Ritter, in commenting on the introduction of a compound acetan- 
ihde powder into the eighth decennial revision of the U. S. Phar- 
macopoeia, VTote that it mattered very little whether the alkahne 
salt be a carbonate of ammonium or sodium or a bicarbonate, as it 
was onh^ added to increase the solubihty of the acetaiiihde. Puckner ^ 
could find no experimental basis for tins, however, and was able to 
show in direct contradiction that no increased solubihty occurred 
in alkahne solutions. Acids, on the other hand, especially strong 
solutions, increased the solubihty to some extent, and he concluded 
therefore that acetanifide is probably even less soluble when taken 
vfith an alkahe because of the partial neutrahzation of the acid gastric 
contents. A further reason for the presence of alkahes in mixtures 
vfitli the antipyi’etics, more particularly antipyrine, is found in the 
occasional gastric irritation that results from their administration, 
aHerczel, ^’ien. med. Wchnschr., 1887 XXXYII, 1022. 
& Kobert, Lehrbuch der Intoxikationen, 1902, 73-74. 
cHall, Druggist Circular, 1891, XXXV, 99. 
Ritter, Joui’. Am. Med. Ass., 1906, XLVII, 683. 
e Puckner, Ibid., 1206. 
