Indapamide

Indapamide is an oral antihypertensive agent. Exactly how it lowers blood pressure has not been fully worked out, but both vascular and renal actions have been implicated. The possible benefits of Indapamide in hypertension include a reduction in cardiac hypertrophy and in the thickening of arterial walls, and prevention of the build-up of the embryonic isoform of fibronectin in coronary vessels. They also include free radical scavenging, which leads to stimulation of vasodilator eicosanoid formation, and an interaction with renal carbonic anhydrase.

In the kidney, Indapamide acts on the proximal segment of the distal tubule. It appears to have natriuretic properties, with sodium and chloride excreted in equivalent amounts, and it has less effect on kaliuresis or uric acid excretion. A noticeable increase in urinary volume is seen in man only at doses above 1.5 mg of Indapamide sustained release tablet a day. Clinical studies have not shown significant changes in plasma sodium levels. Significant hypokalemia (plasma potassium <3.2 mmol/L) has been reported in 4% of patients.

Absorption: The released fraction of Indapamide is absorbed rapidly and completely from the gastrointestinal tract. Taking it with food slightly increases the rate and extent of absorption, but these changes are unlikely to matter clinically. After a single dose, the peak serum level occurs about 12 hours after ingestion. Repeated dosing reduces the variation in serum levels between 2 doses.

Distribution: Indapamide spreads widely through the body and binds extensively to some specific sites. In blood it is highly bound to red blood cells (80%), and more specifically to carbonic anhydrase (98%), without significantly inhibiting this enzyme. Binding to plasma proteins is 79%. The plasma elimination half-life is 14 to 24 hours (mean 18 hours), and the volume of distribution is approximately 60L. Steady state is reached after 7 days, and repeated dosing does not lead to accumulation.

Metabolism: The liver metabolizes Indapamide extensively. Only 5 to 7% of the dose is excreted in the urine as unchanged drug.

Elimination: Elimination is mainly through the urine (70% of the dose) and the faeces (22%), in the form of inactive metabolites.