Studies on a New Oral Diuretic: 4-Chloro-3-sulfamylbenzoic Acid 2,2-Dimethylhydrazide

¹ Departments of Pharmacology and Clinical Investigation, Parke, Davis & Company Research Division, Ann Arbor, Michigan.

CI-546 is an acutely effective diuretic, natriuretic, and chloruretic agent in rats, dogs, monkeys, and man. The evidence in dogs suggests that the initial diuretic effect is a tubular phenomenon and that carbonic anhydrase inhibition only becomes an important factor at high dose levels.

On daily oral administration, CI-546 was well tolerated at effective dose levels by rats, dogs, and monkeys for periods of up to 13 weeks.

In normal human beings, CI-546 was well tolerated at daily doses ranging from 20 to 320 mg. Within this dose range, it induced diuresis, natriuresis, and chloruresis. In general, kaliuresis did not occur to any marked degree, and a favorable sodium-potassium ratio was maintained.

The suitable therapeutic dosage in human beings will probably range between 20 and 80 mg. per day, provided edematous subjects respond as the normal subjects used in this study did.

Note:

We would like to recognize the helpful co-operation of Drs. Milton L. Hoefle and H. A. Dewald, the inventors, and Miss Ann Holmes for synthesis of CI-546; of Dr. Austin Stough, McAlester, Oklahoma, for conducting the clinical trials; of Mr. R. A. Fisken, Dr. T. F. Reutner, Mr. D. E. Roll, Mr. J. Schardein, and Dr. 0. J. Sorenson for aid in the toxicity tests; and of Dr. J. M. Vandenbelt and Mr. R. B. Scott for some of the electrolyte assays.

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