Chemical formula: C₁₆H₁₆ClN₃O₃S Molecular mass: 365.835 g/mol PubChem compound: 3702
Indapamide is a sulfonamide derivative with an indole ring, pharmacologically related to thiazide diuretics, which acts by inhibiting the reabsorption of sodium in the cortical dilution segment. It increases the urinary excretion of sodium and chlorides and, to a lesser extent, the excretion of potassium and magnesium, thereby increasing urine output and having an antihypertensive action.
Phase II and III studies using monotherapy have demonstrated an antihypertensive effect lasting 24 hours. This was present at doses where the diuretic effect was of mild intensity.
The antihypertensive activity of indapamide is related to an improvement in arterial compliance and a reduction in arteriolar and total peripheral resistance.
Indapamide reduces left ventricular hypertrophy.
Thiazide and related diuretics have a plateau therapeutic effect beyond a certain dose, while adverse effects continue to increase. The dose should not be increased if treatment is ineffective.
It has also been shown, in the short-, mid- and long-term in hypertensive patients, that indapamide:
Indapamide 1.5 mg is supplied in a prolonged release dosage based on a matrix system in which the drug substance is dispersed within a support which allows sustained release of indapamide.
The fraction of indapamide released is rapidly and totally absorbed via the gastrointestinal digestive tract.
Eating slightly increases the rapidity of absorption but has no influence on the amount of the drug absorbed.
Peak serum level following a single dose occurs about 12 hours after ingestion, repeated administration reduces the variation in serum levels between 2 doses. Intra-individual variability exists.
Indapamide 2.5 mg is rapidly and completely absorbed after oral administration. Peak blood levels are obtained after 1 to 2 hours.
Binding of indapamide to plasma proteins is 79%.
The plasma elimination half-life is 14 to 24 hours (mean 18 hours).
Steady state is achieved after 7 days.
Repeated administration does not lead to accumulation.
Indapamide is concentrated in the erythrocytes and is 79% bound to plasma protein and to erythrocytes. It is taken up by the vascular wall in smooth vascular muscle according to its high lipid solubility.
Elimination is essentially urinary (70% of the dose) and faecal (22%) in the form of inactive metabolites.
70% of a single oral dose is eliminated by the kidneys and 23% by the gastrointestinal tract. Indapamide is metabolised to a marked degree with 7% of the unchanged product found in the urine during the 48 hours following administration. Elimination half-life (β phase) of indapamide is approximately 15-18 hours.
Pharmacokinetic parameters are unchanged in renal failure patients.
Indapamide has been tested negative concerning mutagenic and carcinogenic properties.
The highest doses administered orally to different animal species (40 to 8000 times the therapeutic dose) have shown an exacerbation of the diuretic properties of indapamide. The major symptoms of poisoning during acute toxicity studies with indapamide administered intravenously or intraperitoneally were related to the pharmacological action of indapamide, i.e. bradypnoea and peripheral vasodilation.
Reproductive toxicity studies have not shown embryotoxicity and teratogenicity.
Fertility was not impaired either in male or in female rats.
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