The Influence of Orally

Haag and Larson (1) demonstrated in 1942 that in the case of nicotine the extent of urinary excretion of a chemical may be related to the reaction of urine. They emphasized the importance of taking into consideration the dissociation constant of a drug and the relative reabsorbability of the free and dissociated base. Extending these studies to the urinary excretion of quinine in man, Haag, Larson and Schwartz (2) found in 1943 that the urinary output could be doubled by passing from an alkaline to an acid urine and they ascribed the difference to greater resorption of quinine from the urinary tract when the urine is alkaline. In connection with studying the behavior of newer antimalarial drugs in man, the extent of the influence of urinary acid-base balance upon renal excretion was re-examined. Parallel studies by Emerson and Dole (3) indicated that renal clearance of quinacrine is subject to 100-fold variations due principally to 2 variables, the urinary pH and the renal plasma flow. Work conducted at the same time by the Army Malaria Research Unit at Oxford (4) emphasized the striking parallelism between urinary excretion of quinacrine and ammonia. They found that the ratio of urinary quinacrine to urinary ammonia is directly proportional to the plasma quinacrine concentration. Trager and Hutchinson (5) in 1946 similarly found the urinary excretion of quinacrine to be closely correlated with the urinary excretion of ammonia. The present investigation was designed to ascertain the effect of oral ingestion of alkali and acid upon the renal excretion of this general type of organic compound. The substances selected