26

     They report that, in the case of those who received the Quinine in a dilu-
tion of 1 in 10, elimination ended within 48 hours after the last injection; and
that in the other case elimination was pronounced for four or five days after the
last injection. It is difficult to explain the differences in elimination shown in.
Tables A and. B. Judging from the in vitro experiments, there is no reason.
why Quinine urea should be better absorbed than Quinine hi-hydrochloride:
It would appear, moreover, that Quinine urea has not fulfilled the hopes
entertained of it; for Giemsa³⁴ has recently recommended the combination of
Quinine hydrochloride with urethane for hypodermic injection. Urethane
and antipyrine increase the solubility of Quinine hydrochloride, new chemical
products being formed from which, it is thought, Quinine is liberated in the
body. Gaglio³⁵ recommended the urethane solution as being neutral, non-irri-
tating and stable: after its hypodermic injection he recovered from 30 to
50 per cent. in the urine and concluded that it was rapidly and completely
absorbed. Schmitz,²¹ however, has been unable to confirm these results ;
giving the urethane solution hypodermically to a patient daily for seven days,
he found the daily amount eliminated was only 16.1 per cent. on an average.
Recently Giemsa³⁴ seems to have given up the use of Quinine-urea in favour of
this urethane solution of Quinine hydrochloride, the advantages he puts forward
for the latter being: that it will stand boiling for an hour and is not de-
composed by heat like Quinine urea while being sterilized, that it is well
absorbed, that it has a similar re-action to that of the tissue fluids and that its
intramuscular injection is almost painless. In the antipyrine solution of
Quinine hydrochloride, quinopyrin is formed, which according to Santesson
is less toxic than Quinine, but according to Stofella is useless.³⁶ Regarding
these solutions resulting in the formation of new compounds Marshall³⁶ states
that they should be looked upon with suspicion. Moreover, it should be noted
that their miscibility with ox blood-serum is no greater than that of solutions
of simple Quinine hydrochloride itself. Solubility in water is merely of advan-
tage during the process of injecting; it is solubility or miscibility in serum that
favours absorption.

     Clinically, one striking pint about the hypodermic administration of
Quinine is the sudden great increase recently in dosage by this method. A few
years ago the hypodermic dose of Quinine was usually given as from four to six
grains; at present the dose is generally from ten to fifteen grains—the same
as when given by the mouth. This indicates that absorption after oral adminis-
tration is at least as complete as after hypodermic. In comparing the two
methods of administration there remains therefore only the question of prompt-
ness of action. Smythe's¹⁴ experience is that after hypodermic injection Quinine
is slowly absorbed and that its elimination takes weeks; that 20 grains injected