"What are diuretics and how do they work?
The amount of fluid (water) retained by the body is controlled primarily by the kidneys. This occurs due to the kidney's ability to control the retention and elimination of sodium and chlorid"...
Indapamide is the first of a new class of antihypertensive/diuretics, the indolines. The oral administration of 2.5 mg (two 1.25 mg tablets) of indapamide to male subjects produced peak concentrations of approximately 115 ng/mL of the drug in blood within two hours. The oral administration of 5 mg (two 2.5 mg tablets) of indapamide to healthy male subjects produced peak concentrations of approximately 260 ng/mL of the drug in the blood within two hours. A minimum of 70% of a single oral dose is eliminated by the kidneys and an additional 23% by the gastrointestinal tract, probably including the biliary route. The half-life of Lozol (indapamide) in whole blood is approximately 14 hours.
Lozol (indapamide) is preferentially and reversibly taken up by the erythrocytes in the peripheral blood. The whole blood/plasma ratio is approximately 6:1 at the time of peak concentration and decreases to 3.5:1 at eight hours. From 71 to 79% of the Lozol (indapamide) in plasma is reversibly bound to plasma proteins.
Lozol (indapamide) is an extensively metabolized drug, with only about 7% of the total dose administered, recovered in the urine as unchanged drug during the first 48 hours after administration. The urinary elimination of 14C-labeled indapamide and metabolites is biphasic with a terminal half-life of excretion of total radioactivity of 26 hours.
In a parallel design double-blind, placebo controlled trial in hypertension, daily doses of indapamide between 1.25 mg and 10.0 mg produced dose-related antihypertensive effects. Doses of 5.0 and 10.0 mg were not distinguishable from each other although each was differentiated from placebo and 1.25 mg indapamide. At daily doses of 1.25 mg, 5.0 mg and 10.0 mg, a mean decrease of serum potassium of 0.28, 0.61 and 0.76 mEq/L, respectively, was observed and uric acid increased by about 0.69 mg/100 mL.
In other parallel design, dose-ranging clinical trials in hypertension and edema, daily doses of indapamide between 0.5 and 5.0 mg produced dose-related effects. Generally, doses of 2.5 and 5.0 mg were not distinguishable from each other although each was differentiated from placebo and from 0.5 or 1.0 mg indapamide. At daily doses of 2.5 and 5.0 mg a mean decrease of serum potassium of 0.5 and 0.6 mEq/Liter, respectively, was observed and uric acid increased by about 1.0 mg/100 mL.
At these doses, the effects of indapamide on blood pressure and edema are approximately equal to those obtained with conventional doses of other antihypertensive/diuretics.
In hypertensive patients, daily doses of 1.25, 2.5 and 5.0 mg of indapamide have no appreciable cardiac inotropic or chronotropic effect. The drug decreases peripheral resistance, with little or no effect on cardiac output, rate or rhythm. Chronic administration of indapamide to hypertensive patients has little or no effect on glomerular filtration rate or renal plasma flow.
Lozol (indapamide) had an antihypertensive effect in patients with varying degrees of renal impairment, although in general, diuretic effects declined as renal function decreased. In a small number of controlled studies, Indapamide taken with other antihypertensive drugs such as hydralazine, propranolol, guanethidine and methyldopa, appeared to have the additive effect typical of thiazide-type diuretics.
Last reviewed on RxList: 10/16/2009
This monograph has been modified to include the generic and brand name in many instances.
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