AmMwch,i9of.rm'}      Standardization  of  Preparations.  113 
mammal,  particularly  the  guinea-pig,  which  is  quite  sensitive  to 
digitalis  and  which  does  not  appear  to  offer  so  wide  a  variation  as  is 
observed  in  testing  this  drug  on  frogs  of  different  kinds  and  at  dif- 
erent  seasons  of  the  year. 
It  was  thought  desirable  also  to  determine  what,  if  any,  relation 
there  was  between  the  lethal  dose  of  a  digitalis  preparation  and  the 
amount  of  digitoxin  present,  which  principle  is  more  easily  deter- 
mined by  chemical  means  than  the  other  principles  accompanying 
it.  The  results  of  these  experiments  will  be  detailed  in  the  second 
portion  of  the  paper. 
Experiments  with  various  preparations  of  digitalis  and  with  the 
active  principle  digitoxin  point  very  clearly  to  the  fact  that  digitoxin 
represents,  if  not  all,  by  far  the  most  important  properties  of  digi- 
talis. 
In  determining  the  lethal  dose  of  any  digitalis  preparation,  guinea, 
pigs  are  selected  of  240  grammes  weight.  The  preparation  to  be 
tested,  if  a  tincture  or  fluidextract,  is  freed  from  the  greater  part  of 
alcohol  by  evaporation  at  a  low  temperature  and  diluted  with  water 
to  the  desired  quantity.  Progressively  increasing  amounts  are 
injected  subcutaneously  into  the  guinea-pig.  A  poisonous  dose  is 
followed  within  twenty  minutes  to  a  half  hour  by  symptoms  of  ex- 
citement in  the  animal.  The  animal  runs  around  its  cage,  trembles, 
and  a  very  decided  nausea  is  present.  This  is  rapidly  followed  by 
convulsions,  which  rapidly  increase  in  intensity  and  in  the  intervals 
between  them.  The  animal  usually  dies  during  one  of  these  con- 
vulsions. It  has  been  observed  after  experiments  on  many  animals 
that  a  dose  of  digitalis  or  its  preparation  which  does  not  kill  the 
animal  within  two  hours  is  never  fatal.  This  has  been  accepted 
arbitrarily  as  a  standard,  and  that  dose  of  digitalis  which  kills  the 
guinea-pig  of  240  grammes  weight  between  an  hour  and  a  half  and 
two  hours  after  administration,  we  fix  as  our  lethal  dose.  Upon 
determining  the  lethal  dose  of  a  given  preparation  by  means  of  a 
series  of  guinea-pigs,  we  take  the  lethal  dose  so  determined  and  ad- 
minister that  amount  to  five  or  six  other  pigs  as  a  control.  With- 
out exception,  we  have  found  that  the  dose  determined  in  a  series 
invariably  kills  the  same  size  pig  under  the  same  conditions. 
How  closely  this  lethal  dose  is  related  to  the  digitoxin  present  in 
a  given  preparation  will  also  be  shown  in  the  second  portion  of  the 
paper.    Our  work  so  far  seems  to  justify  us  in  using  the  toxic  dose 
