Chlorthalidone has an intrinsic hypotensive effect which is independent of its natriuretic effect, but it does not cause a fall in blood pressure in normotensive persons. In humans chlorthalidone is completely absorbed after oral administration and is excreted unchanged in the urine. Studies in the experimental animal indicate that chlorthalidone is taken up by the tissues rather rapidly. Studies of tissue concentration indicated the compound is concentrated in the kidney and disappears more slowly from this organ than from other organs. Somewhat lower concentrations were found in the liver, myocardium, lung and spleen, but none could be detected in nervous or adipose tissue.
Chlorthalidone is very resistant to metabolic breakdown.
The mode of action of all the newer sulfonamide diuretics, including chlorthalidone, is still not completely clear. Chlorthalidone does not exercise any significant effect on either paramino-hippuric acid clearance or on creatinine clearance and hence exerts no effects on either renal circulation or glomerular filtration. Its site of action must therefore be sought in the renal tubules. The response to chlorthalidone differs sharply from that of acetazolamide, the action of which has been attributed to inhibition of carbonic anhydrase. Moreover, chlorthalidone enhances sodium and chloride excretion in an almost parallel manner and affects potassium excretion to a lesser degree.