Sign Out
Pharmacology: Pharmacodynamics: 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.
Amlodipine is a calcium ion influx inhibitor of the dihydropyridine group (slow channel blocker or calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle.
The mechanism of the antihypertensive action of amlodipine is due to a direct relaxant effect on vascular smooth muscle.
Pharmacokinetics: The co-administration of indapamide and amlodipine does not change their pharmacokinetic properties by comparison to separate administration.
Indapamide: Indapamide 1.5 mg is supplied in a prolonged release dosage based on a matrix system in which the active substance is dispersed within a support which allows sustained release of indapamide.
Absorption: 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 active substance 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.
Distribution: 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.
Elimination: Elimination is essentially urinary (70% of the dose) and fecal (22%) in the form of inactive metabolites.
High risk individuals: Pharmacokinetic parameters are unchanged in renal failure patients.
Amlodipine: Amlodipine is supplied in an immediate release dosage.
Absorption, distribution, plasma protein binding: After oral administration of therapeutic doses, amlodipine is well absorbed with peak blood levels between 6-12 hours post dose. Absolute bioavailability has been estimated to be between 64 and 80%. The volume of distribution is approximately 21 l/kg. In vitro studies have shown that approximately 97.5% of circulating amlodipine is bound to plasma proteins.
The bioavailability of amlodipine is not affected by food intake.
Biotransformation/elimination: The terminal plasma elimination half-life is about 35-50 hours and is consistent with once daily dosing. Amlodipine is extensively metabolized by the liver to inactive metabolites with 10% of the parent compound and 60% of metabolites excreted in the urine.
Use in hepatic impairment: Very limited clinical data are available regarding amlodipine administration in patients with hepatic impairment. Patients with hepatic insufficiency have decreased clearance of amlodipine resulting in a longer half-life and an increase in AUC of approximately 40-60%.
Use in older people: The time to reach peak plasma concentrations of amlodipine is similar in elderly and younger subjects. Amlodipine clearance tends to be decreased with resulting increases in AUC and elimination half-life in elderly patients. Increases in AUC and elimination half-life in patients with congestive heart failure were as expected for the patient age group studied.
