319 



The Determination of the Minimal Lethal Dose of various Toxic 

 Substances and its Relationship to the Body Weight in Warm- 

 Blooded Animals, together with Considerations bearing on 

 the Dosage of Drugs. 



By Georges Dreyer, M.D., Fellow of Lincoln College, Professor of Pathology 

 in the University of Oxford ; and E. W. Ainley Walker, D.M., Fellow 

 and Tutor of University College, Lecturer in Pathology in the University 

 of Oxford. 



(Communicated by Prof. C. S. Sherrington, F.R.S. Received November 22, 1913, 



—Read January 22, 1914.) 



(From the Department of Pathology, University of Oxford.) 



In the course of investigations on the production, distribution, and rate of 

 disappearance in the body of immune substances, we were occupied in 1908 

 and previous years with a series of experiments on agglutinins, and we 

 arrived at conclusions pointing to their close relationship to the blood and 

 blood-forming organs (1, 2). In association with these inquiries, one of us 

 (G. D.), together with W. Ray, published a communication on the relation- 

 ship between the blood volume and the distribution of agglutinins within 

 the circulation (3). 



It was there shown that the concentration of this substance (agglutinin) 

 in the blood after inoculation into an animal was proportional to the body 

 surface of the animal concerned, and was thus approximately proportional to 

 the two-thirds power of the weight. Hence was deduced the conclusion that 

 the blood volume of the animals examined was proportional to their body 

 surface. 



The recognition of this relationship between surface and blood volume 

 made it clear that the assumptions hitherto made use of in attempting to 

 determine dosage for the administration of therapeutic substances such as 

 antitoxins and drugs required complete revision, at any rate, in so far as 

 the activity of these substances might be supposed to be dependent on their 

 concentration in the circulating blood. Subsequently the surface relation 

 (W«) was taken up by B. Moore (4) in an interesting communication dealing 

 with the dosage of drugs, and especially with the therapeutic action of 

 atoxyl and various other compounds of the heavy metals in the treatment of 

 trypanosomiasis. Moore came to the conclusion that, in regard to these 

 drugs, tolerance was limited by the surface area of the mucous membrane of 



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