Indapamide: clinical pharmacology, therapeutic efficacy in hypertension, and adverse effects

Indapamide will soon be marketed in the United States as an oral antihypertensive agent and diuretic. Its molecular structure includes both a polar sulfamoyl chlorobenzamide moiety and a lipid-soluble methylindoline moiety. It differs chemically from the thiazides in that it does not possess the thiazide ring system and it contains only one sulfonamide group. Indapamide is rapidly and well absorbed after oral ingestion, and it has a long terminal half-life in whole blood which permits once daily administration. Indapamide is extensively metabolized by the liver with excretion of unchanged drug accounting for approximately 5% of the total dose. Although indapamide is thought to exert its antihypertensive effect by its diuretic action, several investigations employing laboratory animal preparations have documented a direct vascular action. It has been categorized as a calcium channel blocking agent and this may account for a portion of its antihypertensive effectiveness. In both the treatment of edema and as an antihypertensive agent, indapamide appears to be comparable to hydrochlorothiazide, chlorthalidone and furosemide and seems to have no clinically important advantage over these agents. Side effects associated with indapamide are minimal and appear to be comparable to those observed with other antihypertensive diuretics. Based on few published studies, indapamide appears to be a useful long acting antihypertensive and diuretic agent that is well tolerated and associated with minimal biochemical abnormalities or side effects.