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Pharmacology: Indapamide is a cortical dilution segment diuretic. It is a thiazide-type diuretic with a sulfonamide moiety and an indole ring. It increases the urinary excretion of sodium and chloride and, to a lesser degree, the excretion of potassium and magnesium, thereby increasing diuresis and exerting an antihypertensive action. Phase II and III studies in monotherapy have demonstrated an antihypertensive effect lasting 24 hrs. This effect is obtained at doses inducing very slight diuretic effects. Its antihypertensive activity is related to an improvement of arterial compliance and a reduction of total peripheral and arteriolar resistance. The vascular action of indapamide can be explained through a reduction of the vascular smooth muscle cell contractility related to a modification of the transmembrane ionic exchange, particularly of calcium; and a stimulation of the synthesis of the vasodilating and hypotensive prostaglandin PGE2. Recent international multicenter study has demonstrated that Natrilix SR 1 tablet daily significantly reduces left ventricular hypertrophy, mainly at cardiac wall (both posterior and septal wall thickness of the left ventricle). Above effects are carried out progressively until the end of 1-year treatment.
The therapeutic effect reaches a plateau beyond a certain dose, while the adverse effects continue to increase. Do not increase the dose in case of inefficacy of treatment.
It also has been demonstrated in hypertensive patients, over the short-, medium- and long-term, that indapamide does not interfere with lipid metabolism (triglycerides, LDL-cholesterol and HDL-cholesterol) and does not interfere with carbohydrate metabolism, even in hypertensive diabetics. Indapamide reduces microalbuminuria.
Pharmacokinetics: Natrilix SR is supplied as a sustained-release formulation, consisting of a matrix system with dispersion of the active ingredient within a support, which allows sustained release of indapamide.
Absorption: The released fraction of indapamide is rapidly and totally absorbed by the gastrointestinal tract. Meals slightly increase the rate of absorption, but do not have any influence on the quantity of drug absorbed. Peak plasma concentrations occur approximately 12 hrs after a single dose. Repeated dosing limits variations in plasma concentrations between 2 doses. Intraindividual variability exists.
Distribution: 79% of the drug is bound to plasma proteins. The elimination half-life is between 14 and 24 hrs (mean: 18 hrs). The steady state is reached after 7 days. Repeated dosing does not induce accumulation.
Metabolism: Indapamide is essentially eliminated in the urine (70% of the dose) and feces (22%) in the form of inactive metabolites.
At-Risk Population: The pharmacokinetic parameters are unchanged for patients with renal failure.
