326 Prof. G. Dreyer and Dr. E. W. A. Walker. 



In case of cold-blooded animals we are not at present able to put forward 

 any definite statement ; but the problems which they present are under inves- 

 tigation. 



As regards the influence of sex in warm-blooded animals, we find an 

 indication in our figures that female animals require a somewhat smaller dose 

 to produce a given effect than male individuals of corresponding weight. 

 This agrees with what has frequently been pointed out as the result of 

 clinical experience. The observation seems to find its explanation in the fact 

 that the blood volume of female animals is slightly smaller (7) than that of 

 males. For both the initial and the maximal concentration in the plasma of 

 any drug administered by a given route in a series of animals of different size 

 and weight will naturally be related to the volume of the plasma. Whatever 

 be the rate at which it is selected from the plasma by particular cells, and 

 whatever be the rate of its elimination from the body, the concentration in 

 the blood plasma of any given substance must at every stage be related to the 

 volume of that plasma in the individual animal concerned. Thus a given 

 dose of any substance administered (in one and the same dilution) will reach 

 a higher effective concentration in those individuals whose blood volume is 

 less than in those in which it is greater. 



The importance of this question of concentration may be illustrated by 

 a reference to the experiments carried out by Hald (19) witli potassium 

 chloride. These showed that in individuals of equal weight the effect of one 

 and the same dose of the active substance was greater, and manifested itself 

 more rapidly, the higher the concentration in which it was given. 



In view of these considerations it becomes of interest to return to the 

 question of the failure encountered in the treatment of trypanosomiasis in 

 large animals with drugs successfully employed in the smaller species. 



If one compares the doses necessary to produce the same concentration of 

 a given drug in the plasma of man and the rat, it can readily be shown that 

 even if a man of 70 kgrm. could be given the same dose per kilogramme as a 

 rat of 140 grin, weight — the figures selected by Moore in his discussion — 

 the concentration of the drug in the man's blood plasma would only be about 

 75 per cent, of that obtained in the rat. Accordingly, the same therapeutic 

 effect could not be produced. Man, however, cannot tolerate anything ap- 

 proaching this degree of dosage, and hence the treatment which is curative 

 in rats becomes inapplicable in the human subject. But even these facts do 

 not, as it seems to us, afford the whole explanation of the difficulty in question. 

 For it appears that differences in tolerance and intolerance to particular sub- 

 stances in different species of animal are of a specific character and cannot be 

 explained merely by relative differences in blood volume and body surface. 



