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Kerner that carbonic acid probably plays an important part in dissolving
Quinine, both in the process of absorption and in the blood. The results of his
experiments also seem to show that ærated water, swallowed with Quinine or
injected with Quinine as an enema, facilitates the absorption of the alkaloid.
Further support is given to Kerner's idea of the importance of carbonic acid as
a solvent by the following experiment, reported by Wood.²⁷ The amount of
pure Quinine that 1,000 parts of blood defibrinated and deprived of its gases at
36°C. can dissolve is only .398 part, which gives a solubility of about 1 in 25,00.
It has been shown above that Quinine alkaloid is soluble 1 part in 625 of
ordinary ox blood-serum.

     6. Single large doses of Quinine or the same amount in divided doses in the
course of the day.—Giemsa and Schaumann⁵ have shown that, with the daily
administration of one gramme of Quinine in one dose, 23.8 per cent. was
eliminated daily in the urine; with the daily administration of .2 gramme
every two hours till five closes were given, the corresponding figure was 27.8
per cent. From this they conclude that Quinine in divided doses is of greater
therapeutic value than in single large doses, as in the former case less Quinine
is destroyed in the body. They therefore support the treatment of malaria by
fractional doses of Quinine, as recommended by Nocht²⁸ and Ufer.²⁹

     With the single large dose the absorption of Quinine for a certain period
of time must have been much greater than could occur at any time after
administration in divided doses. With the abrupt accentuated absorption from
the single large dose, it is reasonable to expect greater cleavage of Quinine by
the protective forces of the body, hence the diminished elimination in the
urine. Further, there is no reason to suppose that the Quinine which under-
goes cleavage is of no therapeutic value before cleavage has occurred; so the
inference of Giemsa and Schaumann that greater elimination in the urine
connoted greater therapeutic value is unwarranted. With single large doses.
Quinine absorption is accentuated for certain intervals of time; with the small
frequently repeated closes absorption is never accentuated, but continues evenly
at a moderate average. The only way to settle the relative therapeutic value
of these two methods of administration is by actual clinical results.
Nocht seems to have obtained good results by giving four grains of Quinine
every two hours, day and night (if awake), but the great majority of physicians
have by experience come to rely more on 15 grains three times daily: in the
former instance about 48 grains are given daily, in the latter 45 grains. Ac -
cording to Wood,²⁷ large doses at intervals have been found in practice better
than small amounts frequently, and this conclusion is supported by observations
made by Councilman³⁰ that large closes entirely destroy the parasite whereas
fractional doses do not.

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