15

These figures show that after intravenous injection less Quinine (totals)
is eliminated in the urine than after either intramuscular injection or oral
administration. As with intravenous injection there can be no doubt about
the Quinine entering the circulation, it is evident that Quinine elimination
in the urine cannot be directly proportional to the amount of Quinine that has
entered the blood. Further, on referring to the amounts of Quinine eliminated
during the first day, it is quite obvious that there is no direct relationship
between the amount of Quinine that has entered the circulation and the
amount that has been excreted: if it be said that elimination varies directly
with absorption, then more Quinine entered the blood after oral administration
than after intravenous; if it be said that elimination varies inversely with
absorption, then more Quinine entered the blood after intramuscular injection
than after intravenous.

     In reality, the amount of Quinine absorbed must be equal to the amount
of Quinine eliminated in the urine plus the amount that has undergone cleavage
in the body. The determination of the amount of Quinine eliminated in the
urine cannot possibly give us any idea of the amount absorbed unless we are
able to determine at the same time the amount that has undergone cleavage
or to satisfy ourselves that the amount that has undergone cleavage is constant.
Under different conditions of Quinine administration, each of these three
factors varies; and as there is no means of estimating the amount of Quinine
that has undergone cleavage in the body the amount of Quinine eliminated in
the urine is quite fallacious as a universal gauge of the amount of Quinine that
has entered the circulation.

     There is, however, another method, namely, that of determining the mini-
mum-lethal dose—which hitherto seems to have escaped notice—which is cap-
able of giving us a rough estimate of the amount of absorption, especially when
comparing different methods of administration of Quinine. The toxicity or
lethality of a substance must be proportional to the rapidity and thoroughness of
its absoption, no matter by what channel or under what conditions the substance
is administered. And, as in calculating the minimum-lethal dose, death must
occur within twenty-four hours, rapidity may be taken as a constant, so
lethality varies directly with thoroughness of absorption.

Oral Administration.

     As already noted, many assume without any definite proof that Quinine
is absorbed chiefly from the stomach. In their opinion Quinine, in whatever
form administered, is converted to some extent into the soluble hydrochlorides