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PubMed1995

Comparison between the effects of indapamide and hydrochlorothiazide on creatinine clearance in patients with impaired renal function and hypertension.

The long-term effects of indapamide or hydrochlorothiazide on blood pressure and renal function were examined in patients with impaired renal function and moderate hypertension. Both drugs controlled hypertension and blood pressure remained normal during the 2 years of the study. Despite this comparable control of hypertension, indapamide therapy was associated with a 28.5 +/- 4.4% increase in creatinine clearance while treatment with hydrochlorothiazide was associated with a 17.4 +/- 3.0% decrease in creatinine clearance. The results of the study indicate that indapamide is superior to hydrochlorothiazide in the treatment of patients with impaired renal function and moderate hypertension.

Body Weight↗
PubMedDate not supplied

Indapamide in the treatment of hypertension in non-insulin-dependent diabetes.

The antihypertensive effect of indapamide, a new thiazide derivative, has a low diuretic effect and a primary action on vascular smooth muscle. It was evaluated in a series of 20 patients with non-insulin-dependent diabetes (age range 47-75 years) who had arterial hypertension of mild to moderate degree treated with hypoglycemic agents and/or diet. Indapamide, 2.5 mg, was given as a single daily dose for 6 months. A statistically significant reduction of systolic and diastolic pressures was observed in both supine and upright positions. This decrease was significant beginning in the first month of therapy (p less than 0.001). No significant modifications of fasting glycemia, postprandial glycemia, and glycosylated hemoglobin were noted. No significant changes were observed in serum sodium, potassium, chloride, calcium, and uric acid. Indapamide is an effective and practical treatment of hypertension of mild to moderate degree in patients with diabetes. The absence of effect on glucose metabolism makes it an especially interesting drug.

Aged↗
PubMedDate not supplied

Serum lipoproteins during treatment with the antihypertensive agent indapamide.

Considering the documented, potentially undesirable influence of various thiazide-type or loop diuretics on serum lipoproteins, we prospectively investigated in 69 men (mean age +/- SEM, 32 +/- 1 years) the metabolic effects of the new diuretic-antihypertensive compound indapamide. Compared to placebo, indapamide (2.5 mg/day) given for 6 to 8 weeks lowered (p less than 0.02 to less than 0.001) blood pressure (supine values from 148/98 +/- 3/2 to 137/93 +/- 3/2) in 29 men with mild to moderate essential hypertension, but not in 40 healthy men. In both groups, significant (p less than 0.05 to less than 0.001) decreases in body weight (-0.8 kg) and plasma potassium (-0.6 mmol/L), and increases in plasma uric acid (+20%), renin activity (+200%), and aldosterone documented good compliance. There were no significant changes in total cholesterol (in all subjects, from 208 +/- 6 to 213 +/- 6 mg/dl), low- or very low-density lipoprotein (VLDL) cholesterol (127 +/- 6 to 129 +/- 6 and 21 +/- 1 to 21 +/- 2 respectively), high-density lipoprotein cholesterol (50 +/- 1 to 51 +/- 1 mg/dl), total triglycerides (Tg) (108 +/- 5 to 112 +/- 6 mg/dl), VLDL-Tg, apoproteins A1 and A2, plasma glucose, epinephrine, norepinephrine, sodium, calcium, magnesium, and creatinine; apoprotein B (84 +/- 2 to 88 +/- 3 mg/dl) and plasma insulin after glucose loading dose tended to be increased minimally. The absence of distinct lipoprotein alterations after short-term indapamide treatment may be of clinical and epidemiological interest.

Adult↗
PubMed2004

Left ventricular hypertrophy in hypertensive patients in Indian primary care: prevalence and effect of treatment with sustained release indapamide.

OBJECTIVE: Epidemiologic studies indicate an ethnic determinant of left ventricular hypertrophy (LVH), but its prevalence in hypertensive Asian Indians at diagnosis is not known. The observation that LVH regression reduces cardiovascular risk independent of blood pressure, suggests that initial antihypertensive treatment, which also regresses LVH is a desirable goal. This study investigates the prevalence of LVH and its regression with indapamide sustained release (Natrilix SR) in untreated Indian hypertensive patients managed in the primary care setting. DESIGN AND METHODS: Randomly selected physicians serving a defined population recruited untreated hypertensive patients to determine prevalence of LVH. All patients then received indapamide SR treatment for 6 months. LVH was assessed by echocardiography. All measurements were centralized and interpreted by a single blinded observer. MAIN OUTCOME MEASURES: The primary treatment outcomes were the percentage of patients whose LVH regressed with treatment and the number of patients who achieved a blood pressure below 140/90 mmHg. RESULTS: Of the 86 patients recruited, 21 (24.4%, 95% confidence interval (CI) 15.3-33.8) had LVH. There were 11 cases (26.2%) in men, 10 (22.7%) in women, and 15 (32.6%) in those above 50 years. Treatment regressed LVH in 16 (76.2%, 95%CI, 58.0-94.4) by a mean of 25.4 g/m2 (95%CI, 2.8-47.7, p< 0.05). Blood pressure was controlled in 71 (82.6%, 95%CI, 74.5-90.6) patients. CONCLUSION: Prevalence of LVH in untreated Indian hypertensive patients is similar to that in white western populations. Initial indapamide SR treatment is effective in both controlling blood pressure and regressing LVH in the primary care setting.

Antihypertensive Agents↗
PubMed1977

A preliminary controlled evaluation of the antihypertensive effect of indapamide.

A controlled, single-blind trial was carried out in 10 hypertensive patients to compare the effectiveness of a single daily dose (2.5 mg to 5 mg) of indapamide with that of placebo. Blood pressure was measured with a bias-free sphygmomanometer. Indapamide produced a significant reduction in mean systolic and diastolic pressures in both supine and erect positions. It was generally well tolerated: few side-effects were reported and no significant changes were noted in laboratory tests. It is concluded that further long-term studies of indapamide are indicated in larger numbers of patients.

Adult↗
PubMed1983

Indapamide and atenolol in the treatment of hypertension: double-blind comparative and combination study.

Fifteen out-patients with moderate hypertension were randomly and sequentially treated with atenolol, indapamide and a combination of the two drugs after a wash-out period of at least 1 week and a 2-week placebo run-in period. The duration of treatment was 4 weeks in each case. The dosage was 2.5 mg indapamide and 100 mg atenolol, in single tablets which were taken at 11.00 hours. All the treatment regimens produced a highly significant (p less than 0.001) reduction in systolic and diastolic, supine and standing blood pressure; these reductions were not significantly different for the single drugs but were significantly greater for the combined therapy. The number of patients reaching the end-point of a diastolic blood pressure of 95 mmHg or less was the same with either atenolol or indapamide, i.e. 7 (46.6%), but was greater with the combined therapy, i.e. 10 (66.6%). A significant (p less than 0.001) reduction in pulse rate was observed with the treatments involving atenolol. Acceptability of the treatments was very good; the number of volunteered and elicited complaints during the different treatments being less compared to the placebo period, particularly for the combined treatment. No significant difference was observed in the blood biochemistry tests. The results are discussed in light of the mechanisms of action of the two drugs, which seem well integrated with each other, and the duration of the antihypertensive effect, which allows a single administration with consequent good treatment compliance.

Adult↗
PubMed1983

Indapamide in the treatment of essential arterial hypertension: results of a controlled study.

A double-blind trial was carried out in 24 patients with mild hypertension to compare the efficacy and tolerability of indapamide with that of a standard thiazide diuretic, hydrochlorothiazide. After a 6-week washout period on placebo, patients received either 2.5 mg indapamide or 50 mg hydrochlorothiazide per day for 12 weeks. Blood pressure and pulse rate in the recumbent and upright positions were monitored at regular intervals. Laboratory measurements of plasma electrolytes, other biochemical and haematological parameters were made before and after active treatment. The results showed that indapamide treatment produced a statistically significant reduction from placebo levels in diastolic pressure in both the upright and recumbent positions, whereas the reduction was significant only in the upright diastolic pressure with hydrochlorothiazide. There were no significant changes in pulse rate in either active-treatment period. Both drugs produced small but significant reductions in mean plasma chloride and potassium levels, and there was a significant increase in mean serum uric acid in patients receiving hydrochlorothiazide. None of these changes, however, were of clinical importance and all of the patients completed the study.

Adult↗
PubMed1983

Antihypertensive effect of indapamide with special emphasis on renal prostaglandin production.

A study was undertaken in 19 patients with benign to moderate essential hypertension to verify the effect of indapamide alone or combined with a beta-blocker on plasma renin activity, plasma aldosterone, serum potassium and urinary prostaglandins PGE2 and PGF2a. Blood pressure was normalized in 11 (58%) patients with 2.5 mg indapamide/day. In the remaining 8 patients, the addition of pindolol resulted in blood pressure control. Under indapamide, a 70% increase in plasma renin activity and 81% (p less than 0.01) in plasma aldosterone was observed, whereas there was an 18% (p less than 0.001) decrease in potassium. Simultaneously, an increase in urinary PGE2 and PGF2a was observed; these values were significant for PGE2 (p less than 0.025). The addition of pindolol did not produce significant change in the biochemical parameters measured. The increase in the excretion rate of primary prostaglandins could play a role in the mode of action of indapamide.

Adult↗
PubMed1985

The efficacy and tolerance of indapamide in essential hypertension: a multi-centre study in 981 patients.

A multi-centre open trial involving 150 cardiologists throughout France was undertaken to assess the efficacy and tolerance of indapamide in the treatment of essential hypertension. An identical protocol was used by all of the cardiologists. A total of 981 patients (mean age 58 years) was included in the trial after an observation period of 1 month during which blood pressure was recorded regularly. Patients were included if they had permanent essential hypertension with a diastolic pressure of 95 mmHg or more. Mean systolic and diastolic blood pressures at the end of the initial observation period were 179/103 mmHg. The treatment period lasted for 4 months during which the patients received 1 tablet of indapamide (2.5 mg) each morning. Blood pressure was measured after 6 and 16 weeks of treatment, and clinical and biological acceptability was also assessed. After 6 weeks of treatment, mean systolic and diastolic blood pressure levels decreased to 158/90 mmHg: after 16 weeks these mean figures were 150/86 mmHg. Blood pressure levels became normal with indapamide treatment alone in 80% of patients. A slight decrease in serum potassium levels was noted in the first 6 weeks of treatment and then became stable. Clinical acceptability was considered good or excellent in 89% of cases and few non-specific side-effects were reported.

Adult↗
PubMed1990

Antidiuretic effect of indapamide in central diabetes insipidus.

Indapamide produced a significant decrease in urinary output in three patients with central diabetes insipidus. The 24-h urinary volume was reduced from 5 to 2.3 l in a 39-year-old woman; from 11 to 4.3 l in a 30-year-old man, and from 16 to 9.2 l in a 40-year-old man receiving 2.5 mg of indapamide per day. To our knowledge, the antidiuretic effect of indapamide in central diabetes insipidus has not been reported previously.

Adult↗
PubMed2001

[Effects of perindopril and its combination with indapamide on risk stratification in patients with hypertension].

AIM: To study effects of perindopril, indapamid and their combination on stratification of essential hypertension (EH) risk factors. MATERIAL AND METHODS: The 10-year risk to develop cardiovascular complications was assessed in 85 EH patients before and after 12 months of treatment with perindopril, indapamid and their combination. RESULTS: The high risk of cardiovascular complications in the above patients reduced by 21.5, 14.8 and 26.6% 12 months after treatment with perindopril, indapamid and their combination, respectively. CONCLUSION: Low risk of cardiovascular complications was related not only with a fall in systolic and diastolic blood pressure but also with positive effect on left ventricular hypertrophy, absence of negative influence on total cholesterol, glucose in blood plasma.

Antihypertensive Agents↗
PubMed2001

Amelioration of arterial properties with a perindopril-indapamide very-low-dose combination.

BACKGROUND: Epidemiological studies have shown that increased arterial stiffness and wave reflections, major determinants of systolic and pulse pressure, are associated with morbidity and mortality. Therapeutic trials based on cardiovascular mortality have recently shown that reduction of systolic blood pressure (SBP) requires normalization of both large-artery stiffness and wave reflections. AIMS: To compare the antihypertensive effects of the very-low-dose combination of perindopril (2 mg) and indapamide (0.625 mg) (one or two tablets per day) with the beta-blocking agent atenolol (50 mg; one or two tablets per day) in order to determine whether the combination decreased SBP and pulse pressure more than did atenolol, and whether this decrease occurred in relation to a reduction in arterial stiffness [aortic pulse wave velocity (PWV)] or a decrease in the intensity of, or delay in, wave reflections (augmentation index, measured by applanation tonometry) or a combination of both. MATERIAL AND METHODS: This was a double-blind randomized study in 471 individuals with essential hypertension followed for 12 months. Arterial pressure was measured in the brachial artery (mercury sphygmomanometer) and in the carotid artery (applanation tonometry). RESULTS: For the same reduction in diastolic blood pressure (DBP), the combination of perindopril and indapamide decreased brachial SBP and pulse pressure significantly more than did atenolol (adjusted differences between groups -6.2 +/- 1.5 and -5.5 +/- 1.0 mmHg, respectively; P < 0.001). This difference was even more pronounced for the carotid than for the brachial artery. Whereas both antihypertensive agents similarly decreased PWV, only the combination significantly attenuated wave reflections. CONCLUSION: Normalization of SBP, pulse pressure and arterial function--a haemodynamic profile known to improve survival significantly in hypertensive populations at high cardiovascular risk--was achieved to a greater extent with a very-low-dose combination of perindopril and indapamide than with atenolol.

Antihypertensive Agents↗
PubMed2003

Effect of indapamide SR on microalbuminuria--the NESTOR study (Natrilix SR versus Enalapril Study in Type 2 diabetic hypertensives with micrOalbuminuRia)--rationale and protocol for the main trial.

In type 2 diabetic hypertensive patients, microalbuminuria can be due to hypertension and/or diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors act preferentially on microalbuminuria due to diabetic nephropathy. The objective is to demonstrate the efficacy of a thiazide-like diuretic, indapamide sustained release (SR), at reducing microalbuminuria in hypertensive type 2 diabetic patients in comparison with an ACE inhibitor, enalapril. The study is an international multicentre, 12-month, randomized, double-blind, controlled, two parallel group study of type 2 diabetic patients with hypertension (140 mmHg < or = systolic blood pressure <180 mmHg and diastolic blood pressure <110 mmHg) and microalbuminuria. Intervention is after a 4-week placebo period, patients with microalbuminuria > or = 20 and < or = 200 microg/min are randomized to indapamide SR 1.5 mg or to enalapril 10 mg once a day for a one-year treatment period. An additional label treatment by amlodipine 5-10 mg (1st step) and atenolol 50-100 mg (2nd step) a day is permitted after 6 weeks of treatment based upon blood pressure response. The main outcome measures are microalbuminuria expressed as urinary albumin to creatinine ratio, albumin fractional clearance, and albumin excretion rate evaluated on overnight urine collections. Secondary criteria are supine and standing systolic, diastolic and mean blood pressure; and biological and clinical safety. This study will complete the knowledge of the efficacy of indapamide SR in hypertension and target organ damage and will provide valuable information on the management of type 2 diabetic hypertensives with microalbuminuria.

Adult↗
PubMed1992

Indapamide-associated Stevens-Johnson syndrome.

Stevens-Johnson syndrome is an acute, inflammatory eruption of the skin and mucous membranes often associated with drug ingestion. A forty-five-year-old woman showed symptoms consistent with Stevens-Johnson syndrome two days after indapamide therapy was begun for the treatment of hypertension. Initial manifestations consisted of headaches, sore throat, cough, and symptoms of conjunctival injection, including redness and swelling. Approximately two weeks later, the patient noted skin eruptions involving the conjunctiva, lips, face, neck, trunk, and extremities. She was treated with cool compresses, antiseptics, ophthalmic antibiotics and steroids, and oral prednisone. Symptoms began to resolve approximately eight days after indapamide was discontinued and treatment was begun. Although rare, Stevens-Johnson syndrome should be considered in the differential diagnosis of a patient with a history of indapamide ingestion who presents with malaise, fever, and skin eruptions.

Female↗
PubMedDate not supplied

Optimization of two flow-injection spectrophotometric methods for the determination of indapamide in pharmaceutical dosage forms.

Multivariate experimental design has been used to optimize 2 flow-injection spectrophotometric methods for the determination of indapamide in pharmaceutical dosage forms, both pure and commercial tablets. The methods are based on the oxidation of this drug with iron (III) in acidic medium and the subsequent formation of an intensive orange-red complex between the liberated iron (II) and 2,2'-bipyridyl or 1,10-phenanthroline reagents. Plackett-Burman designs were applied as a screening method to evaluate the most significant factors with few experiments. Central composite 2(3)+ star designs were performed to evaluate the response surfaces. The methods have been fully validated and were applied successfully to the determination of indapamide in pure and pharmaceutical forms with good accuracy and precision. Therefore, the 2 proposed procedures are simple, inexpensive, and rapid flow methods for the routine determination of indapamide in pharmaceutical preparations.

Antihypertensive Agents↗
PubMed2006

[Effect of twelve-month combined therapy with perindopril and indapamide on the level of blood pressure and left ventricular hypertrophy in patients with hypertensive disease].

Left ventricular hypertrophy (LVH) in patients with hypertensive disease is associated with unfavorable prognosis. Long term and effective antihypertensive therapy is capable to cause reverse development of LVH. We included in this study 72 patients (27 men, 45 women, age from 34 to 72 years) with untreated 1st and 2nd degree arterial hypertension (systolic blood pressure 140-179 mm Hg and/or diastolic blood pressure 99-109 mm Hg) and echocardiographical signs of LVH (left ventricular myocardial mass index >120 g/m2 in men and >100 g/m2 in women). After that the patients were randomized into 2 groups: the study group (39 patients, mean age 53.0+/-11.6 years) received combination of perindopril and indapamide in initial dose of 2 mg/0.625 mg, and comparison group (33 patients, mean age 54.4+/-8.2 years) received monotherapy with enalapril (10 mg). Once daily dosing of the preparation provided high level of compliance of patients with treatment. During 12-month therapy with combination of perindopril and indapamide target blood pressure (<140/90) was achieved in 74.4% of patients, during monotherapy with enalapril--in 27.3% of patients. Significant decrease of left ventricular myocardial mass index (LVMMI) with combination therapy was observed by 6th month of treatment (from 260 to 234 g), with monotherapy within same period of time--from 267 to 260 g. As a result of 12 months therapy of patients with I-II degree of hypertension with perindopril and indapamide LVMMI decreased by 17.5% while monotherapy with enalapril was associated with 5.6% decrease of LVMMI. Lowering of LVMMI occurred mainly at the account of decrease of left ventricular wall thickness.

Adult↗
PubMed1991

Diuretic agents related to indapamide. IV--Synthesis and pharmacological activity of N-(4-chloro-3-sulfamoylbenzamido)-methyl-phenyl-pyrrolidines and N1-(4-chloro-3-sulfamoylbenzoyl)-N2-aryl- or aralkyl-alkyl-hydrazines.

A series of N(4-chloro-3-sulfamoylbenzamido) derivatives (6 a-c, 10, 11, 12), structurally related to indapamide and isoindapamide, were synthesized and tested for their diuretic and saluretic activity. In addition, the antihypertensive activity of the most interesting term trans 6a was studied on spontaneously hypertensive rats. All tested compounds with the exception of 10 showed diuretic activity comparable to or higher (trans 6 a) than that of indapamide, taken as reference drug. The antihypertensive activity of trans 6 a was comparable to that of indapamide in potency, but its onset of action was slower.

Animals↗
PubMed1988

Platelet alpha 2-adrenoceptor modifications induced by long-term treatment with indapamide in essential hypertension.

The effect of long-term treatment with indapamide in platelet alpha 2-adrenoceptors has been evaluated in 10 patients with essential hypertension, in a double-blind, cross-over study with placebo. After three months of therapy, indapamide significantly reduced mean blood pressure (from 137 +/- 12 to 116 +/- 6 mm Hg, p less than 0.001), whereas heart rate did not change (from 72 +/- 8 to 73 +/- 7 beats/minute). At the same time, platelet alpha 2-adrenoceptor number increased (from 168.2 +/- 48.4 to 256.8 +/- 14.5 fmol/mg protein, p less than 0.02), whereas the dissociation constant did not change (from 3.79 +/- 2.9 to 4.97 +/- 4.48). The plasma norepinephrine level was significantly reduced after long-term treatment with indapamide (from 275 +/- 118 to 210 +/- 56 pg/ml, p less than 0.02). These results bring about an inhibition of norepinephrine release from sympathetic nerve endings with a likely secondary increase of the number of platelet alpha 2-adrenoceptors.

Adult↗