STUDIES ON THE CHEMOTHERAPY OF THE HUMAN MALARIAS. IV. THE METABOLISM OF CINCHONINE IN RELATION TO ITS ANTIMALARIAL ACTIVITY 123

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Abstract
Of orally administered cinchonine, less than 5% can be recovered in the urine as such, and more than 50% as the 2-hydroxy derivative. Higher plasma 2-hydroxy cinchonine than cinchonine levels are achieved when cinchonine alone is administered or when equal doses of the 2 drugs are given. The differences in plasma drug levels and urine excretions of cinchonine and 2-hydroxy cinchonine are chiefly the result of the more rapid rate of metabolism of cinchonine. The main route of cinchonine metabolism proceeds through the 2-hydroxy derivative, its first metabolic product. On the basis of plasma drug levels, 2-hydroxy cinchonine is only one-tenth as active an antimalarial as cinchonine. The major portion of the antimalarial effect achieved when cinchonine is administered is attributable to cinchonine itself and not to any of its metabolic products.