Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: sulfonamides, plain;
ATC code: C03 BA11.
Indapamide is a non-thiazide sulphonamide with an indole ring, belonging to the diuretic family. At the dose of 2.5 mg per day indapamide exerts a prolonged antihypertensive activity in hypertensive human subjects.
Dose-effect studies have demonstrated that, at the dose of 2.5 mg per day, the antihypertensive effect is maximal and the diuretic effect is sub-clinical.
At this antihypertensive dose of 2.5 mg per day, indapamide reduces vascular hyperactivity to noradrenaline in hypertensive patients and decreases total peripheral resistance and arteriolar resistance.
The implication of an extrarenal mechanism of action in the antihypertensive effect is demonstrated by maintenance of its antihypertensive efficacy in functionally anephric hypertensive patients.
The vascular mechanism of action of indapamide involves:
• a reduction in the contractility of vascular smooth muscle due to a modification of transmembrane ion exchanges, essentially calcium; • vasodilation due to stimulation of the synthesis of prostaglandin PGE2 and the vasodilator and platelet antiaggregant prostacyclin PGI2;
• potentiation of the vasodilator action of bradykinin.
It has also been demonstrated that in the short-, medium- and long-term, in hypertensive patients, indapamide:
• reduces left ventricular hypertrophy;
• does not appear to alter lipid metabolism: triglycerides, LDL-cholesterol and HDL-cholesterol;
• does not appear to alter glucose metabolism, even in diabetic hypertensive patients. Normalisation of blood pressure and significant reduction in microalbuminuria have been observed after prolonged administration of indapamide in diabetic hypertensive subjects.
Lastly, The co-prescription of indapamide with other anti-hypertensives (beta- blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors) results in an improved control of hypertension with an increased percentage of responders compared to that observed with single-agent therapy.

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
Absorption
Indapamide is rapidly and completely absorbed after oral administration. Peak blood levels are obtained after 1-2 hours.
Distribution
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
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 (ß phase) of indapamide is approximately 15 – 18 hours.