Effects of Captopril, Hydrochlorothiazide, and Their Combination on Timed Urinary Excretions of Water and Solutes

The effects of single doses of captopril 100 mg, hydrochlorothiazide 25 mg, and a combination of both on 24-h outputs of fluid and several solutes were compared in healthy volunteers. Thirteen subjects were studied in a metabolic ward under strictly controlled conditions. Single doses of placebo, captopril, hydrochlorothiazide, and a combination of captopril and hydrochlorothiazide were given double-blind in random order on 4 separate days. Urine was collected at regular intervals for 24 h after medication. The combination of captopril and hydrochlorothiazide and hydrochlorothiazide alone significantly increased the 24-h urinary outputs of Cl-, Na+, fluid, and K+ compared with placebo and also accelerated the corresponding urinary flows. Captopril did not change the 24-h urinary excretions of Cl-, Na+, fluid, and K+ significantly, though it advanced the time courses of their urinary flows. All medications significantly increased the 24-h renal outputs of Mg2+ and creatinine. Captopril significantly increased the 24-h urinary output of urate and advanced its urinary flow. Hydrochlorothiazide significantly decreased the output and retarded the flow. The combination of captopril and hydrochlorothiazide did not change the 24-h urinary output and retarded its flow. It is concluded that the renal excretory actions of captopril are more prolonged than the plasma levels of the drug would indicate. Captopril has diuretic effects which may vary in potency with aldosterone concentrations and uricosuric properties unrelated to aldosterone status.