io8 
Therapeutic  Virtues  of  Digitalis. 
/  Am.  Jour.  Pharm* 
\      March,  1908. 
represented  the  drug,  then  the  fatal  dose  of  the  principle  should 
correspond  to  the  amount  chemically  found  in  the  single  dose  of  the 
crude  drug.  Unfortunately,  as  far  as  I  know,  there  has  been  no 
such  study  made  of  digitalis,  and  we  have  to  rely  upon  more  or  less 
indirect  evidence.  For  instance,  in  the  research  carried  out  some 
years  ago  (Amer.  Joum.  Medical  Sciences,  August,  1900)  by  Dr. 
Arnold  and  myself  we  found  that  the  average  dose  of  digitalis 
immediately  fatal  was,  for  a  dog,  0*15  gramme  per  kilo  of  body 
weight,  and  that  the  fatal  dose  of  Merck's  digitoxin  was  about  3 
milligrammes  per  kilo.  The  average  content  of  digitalis  leaves  in 
digitoxin  would  seem  to  be,  frcm  various  reports,  between  015  and 
0*3  of  1  per  cent.;  if  we  allow  0-2  per  cent,  as  an  average,  in  the 
fatal  dose  of  digitalis  for  a  dog  there  would  be  contained  but  0-3 
milligramme,  or  about  one-tenth  of  the  quantity  of  digitoxin 
required  to  kill.  These  figures,  for  the  reasons  just  mentioned,  would 
not  in  themselves  be  convincing,  but  they  find  confirmation  in  clini- 
cal experience  which  makes  them  very  suggestive.  From  the 
reports  of  a  considerable  number  of  authors  it  would  seem  that 
from  clinical  experience  0-5  milligramme  may  be  regarded  as  the 
average  therapeutic  dose  of  digitoxin1  corresponding  to  the  effects 
of  0-06  gramme  of  digitalis  leaves.  This  quantity  of  digitalis  leaves, 
however,  would  contain  but  0-12  milligramme,  so  that  while  the  dis- 
crepancy is  not  quite  so  great  as  in  our  experiments,  there  is  still 
a  difference  of  more  than  400  per  cent,  to  be  accounted  for. 
It  would  seem  evident,  therefore,  that  digitoxin  does  not  repre- 
sent in  activity  more  than  one-fourth  of  the  power  of  digitalis,  and 
any  assay  process  of  digitalis  based  upon  the  quantity  of  digitoxin 
it  contains,  discards  three-fourths  of  the  active  substance  of  the 
plant.  As  rational  would  it  be,  apparently,  to  assay  opium  for  the 
codeine  in  it,  neglecting  the  morphine,  as  to  assay  digitalis  for  its 
digitoxin  alone. 
If  digitoxin  possesses  the  precise  physiological  and  therapeutic 
properties  of  digitalis  leaf,  the  mere  quantitative  difference  becomes  a 
matter  of  minor  importance,  since  it  only  necessitates  the  giving  of  a 
comparatively  large  amount.  But  this  does  not,  from  our  present 
knowledge,  seem  to  be  the  case.    One  of  the  most  interesting  re- 
1  See  Wenzel  {Therap.  Monatsch.,  1S95,  ix),  Von  St  arc  k(  Ibid.),  Masius  {Bull. 
Acad.  Roy.  Belg.,  1893,  vii),  Curioni  [Clin.  Med.  Hal.,  1901),  etc. 
