Am.  Jour.  Pharm. ) 
May,  1911.  / 
Standardization  of  Digitalis. 
205 
.  .  .  occasionally  in  mamimals  the  respiration  ceases  before  the  heart 
has  come  to  a  standstill.  This  does  not  indicate  any  direct  action 
of  the  drug  on  the  respiratory  centres,  but  is  due  to  interference  with 
the  function  of  the  medulla,  dependent  on  the  disturbance  of  its 
blood-supply.  The  death  is  thus  due  to  the  stimulating  action  on 
the  heart,  however  it  may  eventually  occur.'' 
The  Philadelphia  committee  find  that  the  only  essential  differ- 
ence in  the  methods  is  that  the  question  of  absorption  plays  an 
important  part  if  frogs  are  used.  They  state  that  Edmunds  and 
Hale  shoiwed  ''the  fatal  dose  for  12  hours  is  about  three-fourths 
of  that  for  one  hour.  It  is  evident  that  the  difference  between  the 
dose  required  to  kill  in  one  hour  and  that  required  to  kill  in  12 
hours  is  largely  a  question  of  rapidity  of  absorption.  Now,  it  may 
easily  be  that  a  preparation  which  is  highly  active  may  be,  for  some 
reason,  comparatively  slowly  absorbed,  so  that  the  one-hour  test 
is  not  only  of  activity  of  the  drug,  but  of  absorbability,  which  is 
manifestly  not  the  purpose  of  the  assay." 
Hatcher  believes  that  the  cat  is  especially  suited  for  the  assay 
of  these  drugs.  By  the  intravenous  administration  of  the  prepara- 
tion to  be  tested,  a  method  simpler,  cheaper,  more  accurate,  and 
less  time-consuming  than  those  usually  employed  is  secured. 
The  simplicity  of  this  method  is  not  very  apparent,  necessitating, 
as  it  does,  anaesthetizing  the  cat,  dissecting  out  the  vein,  and  in- 
sertion of  a  canula.  It  has  not  been  our  experience  that  cats  are 
cheap  or  easily  obtained.  According  to  the  tables  Hatcher  gives, 
with  digitalinum  verum  there  was  an  error  of  20  per  cent. ;  with 
digitalin,  of  over  55  per  cent. ;  with  impure  adonin,  of  9  per  cent. 
Further,  in  a  note  he  says :  ...  we  have  found  a  number  of  cats 
which  tolerated  doses  up  to  nearly  50  per  cent,  more  than  that 
stated."  The  actual  time  of  one  assay  is  90  minutes,  but  when  it 
is  realized  that  a  certain  amount  of  preliminary  preparation  is 
needed,  it  is  evident  that  running  two  animals^,  the  minimum  number 
from  which  reliable  results  could  be  obtained,  will  consume  over 
three  hours. 
That  these  experienced  pharmacologists  should,  after  mature 
consideration,  come  to  such  conclusions  is  a  fact  that  makes  me 
hesitate  to  take  a  contrary  view.  It  does  appear,  however,  that 
certain  points  in  favor  of  the  frog  methods  have  not  been  fully 
brought  out ;  nor  have  certain  important  draw-backs  to  the  mam- 
malian method  been  given  the  prominence  that  is  proper.  Moreover, 
