Description
Indapamide(26807-65-8) is a derivative of benzolsulfonamide and its mechanism of action is analogous to
that of thiazides. It is intended for lowering arterial blood pressure and as an adjuvant drug for
treating edema caused by cardiac insufficiency.
Chemical Properties
Crystalline Solid
Originator
Natrilix,Pharmacodex,W. Germany,1976
Definition
ChEBI: A sulfonamide formed by condensation of the carboxylic group of 4-chloro-3-sulfamoylbenzoic acid with the amino group of 2-methyl-2,3-dihydro-1H-indol-1-amine.
Manufacturing Process
A total of 8.9 parts of 3-sulfamyl-4-chloro-benzoylchloride in a solution of 50
parts of anhydrous tetrahydrofuran are added portionwise in the course of 60
minutes, while stirring, to a solution of 5.2 parts of N-amino-2-methyl indoline
and 3.5 parts of triethylamine in 150 parts of anhydrous tetrahydrofuran. The
reaction mixture is left to stand 3 hours at room temperature, then the
precipitated chiorhydrate of triethylamine is filtered off. The filtrate is
evaporated under vacuum and the residue is crystallized from a solution of 60
parts of isopropanol in 75 parts of water. There are obtained 9 parts of N-(3-
sulfamyl-4-chlorobenzamido)-2-methyl indoline, MP (K) 184° to 186°C, MP
(MK) 160° to 162°C (isopropanol/water). [The melting points beingdetermined on a Kofler heater plate under the microscope (MK) or on a Kofler
Bank (K)].
Brand name
Lozol
(Sanofi Aventis).
Therapeutic Function
Diuretic Indapamide
Clinical Use
Indapamide(26807-65-8) is an effective
diuretic drug when GFR falls below 40 mL/min. The duration of action is approximately 24 hours, with the normal oral adult dosage starting at 2.5 mg given each morning.
The dose may be increased to 5.0 mg/day, but doses beyond this level do not appear to provide additional results.
Side effects
Effects on urine content and side effects are similar to
effects induced by thiazide diuretics.
Synthesis
Indapamide, 4-chloro-N-(2-methyl-1-indolinyl)-3-sulfamoylbenzamide
(21.3.33), is synthesized from 2-methylendoline, the nitrosation of which gives 2-methyl-
1-nitrosoindoline (21.3.31). Reducing this with lithium aluminum hydride leads to formation
of 1-amino-2-methylendoline (21.3.32). Acylating this with 3-sulfonylamino-4-chlorbenzoic
acid chloride leads to (21.3.33).
Drug interactions
Potentially hazardous interactions with other drugs
Analgesics: increased risk of nephrotoxicity with
NSAIDs; antagonism of diuretic effect.
Anti-arrhythmics: hypokalaemia leads to increased
cardiac toxicity; effects of lidocaine and mexiletine
antagonised.
Antibacterials: avoid administration with
lymecycline.
Antidepressants: increased risk of hypokalaemia
with reboxetine; enhanced hypotensive effect with
MAOIs; increased risk of postural hypotension with
tricyclics.
Antiepileptics: increased risk of hyponatraemia with
carbamazepine.
Antifungals: increased risk of hypokalaemia with
amphotericin.
Antihypertensives: enhanced hypotensive effect;
increased risk of first dose hypotension with postsynaptic
alpha-blockers like prazosin; hypokalaemia
increases risk of ventricular arrhythmias with sotalol.
Antipsychotics: hypokalaemia increases risk
of ventricular arrhythmias with amisulpride;
enhanced hypotensive effect with phenothiazines;
hypokalaemia increases risk of ventricular
arrhythmias with pimozide - avoid.
Atomoxetine: hypokalaemia increases risk of
ventricular arrhythmias.
Cardiac glycosides: increased toxicity if hypokalaemia
occurs.
Ciclosporin: increased risk of nephrotoxicity and
possibly hypomagnesaemia.
Cytotoxics: increased risk of ventricular arrhythmias
due to hypokalaemia with arsenic trioxide; increased
risk of nephrotoxicity and ototoxicity with platinum
compounds.
Lithium excretion reduced (increased toxicity).
Metabolism
Indapamide is strongly bound to red blood cells, and
is taken up by the vascular wall in smooth vascular
muscle according to its high lipid solubility. 60-70% of
a single oral dose is eliminated by the kidneys and 23%
by the gastrointestinal tract. Indapamide is extensively
metabolised with 5-7% of unchanged drug found in
the urine during the 48 hours following administration.
About 16-23% of dose is excreted in the faeces
