Chlorothiazide in doses of 1 Gm. by mouth twice daily induced the excretion of practically the same amounts of sodium and chloride as did 2 cc. of a molar solution of meralluride injected intravenously. When the chlorothiazide was administered daily for two or three weeks, the sodium excretion declined until it approached the daily intake, and the patient's body weight approached a steady level about 4 lb. (1.8 kg.) below the initial level. A nearly maximal rate of sodium excretion was obtained with 2 Gm. of either chlorothiazide or flumethiazide, and increasing the doses to 4 Gm. did not yield further significant increases of sodium excretion. For hydrochlorothiazide the dose required to give maximum excretion rates was 200 mg. A steadier effect and over-all increase in response resulted from giving doses of 200 mg. of hydrochlorothiazide every 12 hours as compared to 400 mg. given once a day.
Moyer JH. HUMAN PHARMACOLOGY OF THIAZIDE DERIVATIVES. JAMA. 1959;170(17):2048–2054. doi:10.1001/jama.1959.03010170010002
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