TISSUE DISTRIBUTION 783 



study of Chance et al. (1945) around 80% of the total administered arsenical 

 is accounted for by excretion within a week, and in most studies a very 

 tightly bound fraction seems to remain for long periods. Hogan and Eagle 

 (1944) found urinary excretion within a 48-hr period to vary between 

 7 and 74% of the injected dose with different phenylarsenoxides. Arsenite 

 behaves somewhat differently than the organic arsenicals. It is apt to 

 be excreted fairly rapidly, as in mice where most of the radioactivity is 

 gone within 12 hr (Born and Timofeeff-Ressovsky, 1941), although in man 

 it may take a few days (Hunter et al., 1942), The excretion seems to be 

 almost entirely renal, neither arsenite nor the organic pentavalents being 

 picked up by the liver and excreted in the bile, as are the organic trivalents. 



Consideration of Some Special Tissues 



Arsenicals injected into the blood stream, or reaching it by other chan- 

 nels, generally leave it rapidly, to be largely excreted if pentavalent or 

 bound in the tissues if trivalent; it was shown over 60 years ago that arsenite 

 at toxic doses leaves the blood stream very rapidly (Morishima, 1900 a), 

 Arsenicals are retained in the blood of the rat more than in other species, 

 and much of it has been shown to be bound to the globin portion of hemo- 

 globin (perhaps 50-60% of that injected) (Hunter and Kip, 1941) so that 

 the erythrocytes must be considered as potential depots for the arsenicals. 

 The high capacity of the erythrocytes for fixing arsenicals was shown 

 by Hogan and Eagle (1944), who incubated rabbit blood and oxophenarsine 

 for various periods. All of the arsenical up to 1,3 raM oxophenarsine is 

 bound, and above this concentration the per cent bound decreases, although 

 the total amount bound increases so that even at 13 vcvM the erythrocytes 

 are not saturated, despite beginning hemolysis. The rate of uptake by the 

 erythrocytes varies with the arsenical: with phenylarsenoxide, equilibrium 

 is reached within 5 min, whereas with oxophenarsine it requires 2 hr 

 — the total amounts taken up, however, are the same. Arsenite and the 

 pentavalents are not taken up readily by the erythrocytes. When oxophen- 

 arsine or dichlorophenarsine is injected intravenously into man, essentially 

 no arsenical can be demonstrated in the blood after 5-15 min (Henning 

 and Kampmeier, 1943). It was calculated by Fink and Wright (1948 a) 

 that the blood concentration of oxoi)henarsine in patients receiving the 

 drug clinically would be around 0.05 rcvM, at which concentration they 

 find about 40% to be bound to the erythrocytes. They believed that the 

 binding is at the cell surface, although their evidence is not valid. They 

 showed that, upon washing the cells, 60-90% is removed and a small frac- 

 tion remains tightly bound. 



Arsenicals penetrate poorly into the central nervous system, a fact 

 often of importance in the treatment of infections, although it is believed 

 that greater penetration may be achieved when inflammation is present. 



