THE EFFECT OF DOSAGE REGIMEN ON THE DIURETIC EFFICACY OF CHLOROTHIAZIDE IN HUMAN SUBJECTS

¹ Food and Drug Building, Ottawa, Canada
² Department of Medicine (Division of Clinical Pharmacology) and Department of Pharmacology and Experimental Therapeutics, The Johns Hopkins University School of Medicine, Baltimore, Maryland

Ten healthy male subjects were subjected to a controlled double blind study to test the hypothesis that the efficacy of chlorothiazide is a function of dosage regimen. The results indicate that spacing of doses is a potent determinant of diuretic effect and that a given amount of chlorothiazide is more effective when split up into smaller doses given intermittently than when administered in a single dose. It is suggested that the question of dosage regimen be given greater attention in the design of trials on diuretic drugs.

In two additional experiments the influence of probenecid on the diuretic efficacy of various dosage regimens of chlorothiazide was also studied. The inconsistent results of these latter experiments suggest that the effect of probenecid on chlorothiazide-induced diuresis is a complex one.