Guidelines for Development of a New Diuretic Agent
Preclinical assessment of a diuretic agent is straightforward with dual goals of identifying the active substance and its site of activity. In addition, one must determine whether the diuretic gains access to its site of action from the blood as opposed to the urine, and depending upon those findings, assess mechanisms by which access to the active site occurs. Both in vivo and in vitro studies are required to assess the specific nephron segment at which the diuretic has activity. These studies are important for predictions as to efficacy and side effects. Knowledge that a diuretic has its effects at a particular nephron site allows prediction of the degree of natriuresis that will occur and also the concomitant excretion of other electrolytes which may impact on adverse effects (e.g., potassium or magnesium).
KeywordsProximal Tubule Fractional Excretion Nephron Segment Diuretic Agent Free Water Clearance
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