Chlorothiazide Derivatives for Diabetes Insipidus?

Abstract

Introduction Crawford and Kennedy¹ demonstrated that orally administered chlorothiazide decreased urine volume and doubled urine osmolality in rats with experimental diabetes insipidus (DI). A similar action was also noted in both acquired and nephrogenic human diabetes insipidus. Heinemann et al.² reported that chlorothiazide produced decreased free water clearance (C_H2O) by inhibiting solute reabsorption at a distal site in the nephron, thus preventing elaboration of solute-free water. However, examination of their data reveals that C_H2O, corrected for decrease in glomerular filtration rate, increased slightly in all but one subject receiving a single 500 mg. intravenous dose of chlorothiazide. The largest increase occurred in a subject with diabetes insipidus, which is in contrast to the results reported following oral administration of chlorothiazide or hydrochlorothiazide to patients with diabetes insipidus. This report deals with the results of intravenously administered chlorothiazide and orally administered hydrochlorothiazide in 2 human subjects with