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At least 145 records · Page 8Linked to original sources
PubMed1988

Cardiovascular effects of indapamide in hypertensive patients with or without renal failure. A dose-response curve.

Fifteen patients with mild-to-moderate hypertension (10 with normal and five with decreased renal function) were studied after treatment with placebo and low (1 mg), intermediate (2.5 mg), and high (5.0 mg per day) doses of indapamide, each for four weeks. Six patients--five with normal renal function--were classified as nonresponders (decrease in diastolic blood pressure less than 5 mm Hg). The remaining nine patients had dose-related decreases in blood pressure. Patients with or without renal failure showed similar decreases in blood pressure. Blood pressure reduction was associated with a significant decrease in cardiac index in the responders at the highest dose, related to a decrease in left ventricular end-diastolic dimension and stroke volume, whereas heart rate did not increase. This apparent decrease in venous return was associated with a significant decrease in body weight but not plasma volume in the responders. Indapamide did not change plasma norepinephrine levels, but decreased pressor responsiveness to exogenous norepinephrine. Responders had lower initial plasma renin activity and a smaller absolute increase in plasma renin activity while receiving indapamide, whereas angiotensin II pressor responsiveness was decreased more. The results presented indicate that the blood pressure lowering effect of indapamide in the present patient population is observed with or without renal failure and is associated with a decrease in pressor reactivity. In nonresponders, compensatory mechanisms (e.g., renin) may negate the antihypertensive effect of indapamide.

Cardiovascular System↗
PubMed1986

Treatment of idiopathic hypercalciuria with indapamide.

Twenty-six patients with idiopathic hypercalciuria (urine calcium level greater than 300 mg/24 h [7.5 mmol/d]) were treated with indapamide (a nonthiazide diuretic), 2.5 mg/d for 3 consecutive months. A mean decrease in urine calcium levels of 52% was noted (p less than 0.05). When therapy with indapamide was stopped, the calcium levels returned to pretherapy values. The effect of indapamide on urine calcium levels was similar to that of hydrochlorothiazide in 10 patients who were receiving the latter drug before therapy with indapamide. The results show that indapamide is an efficient drug for the treatment of idiopathic hypercalciuria.

Aged↗
PubMed1983

Lack of effect of bilateral nephrectomy on the pharmacokinetics of 14C-indapamide (REV 2555) and its metabolites in the dog.

Renal impairment can affect the disposition of metabolites, as well as unchanged drug, especially when there is significant renal clearance of metabolites. The pharmacokinetics of indapamide, a highly metabolized drug, and total indapamide equivalents (as an indicator of metabolites plus unchanged drug) were determined in the anephric dog. An intravenous dose of 14C-indapamide was administered to dogs first after a sham-operation, and then following bilateral nephrectomy. The disposition of total indapamide equivalents, calculated from total radioactivity, was not substantially different after nephrectomy as compared to after sham-operation, with an increase after nephrectomy in the area under the blood level curve (+26.2%), and decreases in the elimination rate constant (-6.9%), volume of distribution (-12.7%) and total blood clearance (-21.9%). The only statistically significant change was the decrease in the volume of distribution. The elimination kinetics of unchanged drug were also qualitatively similar in both cases. After nephrectomy, a decrease was seen in the elimination rate constant (-10.9%) and the volume of distribution (-16.3%) while slight increases in the total blood clearance (+1.9%) and the area under the blood level curve (+4.8%) were noted. These findings could have important implications for advantageous use of indapamide in treatment of hypertensive patients with renal failure since these data suggest that metabolites as well as unchanged drug could still be effectively eliminated by an alternate, non-renal route, thus minimizing accumulation of these compounds.

Animals↗
PubMed1993

Study of antiatherogenic properties of indapamide in a pharmacologic model.

A localized atheromatous plaque was induced in rabbits after transmural electrical stimulation of the carotid and a cholesterol-rich diet (1.33% cholesterol) for 4 weeks. This model was used to investigate the antiatherogenicity of indapamide. The treatment given per os started 14 days before the stimulation period. Animals were divided into six groups: group 1 (control) received gelatin 2%, group 2 received hydrochlorothiazide at 20 mg/kg/day, group 3 was treated with flunarizine at 25 mg/kg/day, and groups 4, 5, and 6 received indapamide at 0.3, 1, and 3 mg/kg/day, respectively. During the experimental period, all rabbits showed similar weight gain, regardless of the treatment. Image analysis showed an antiatherogenic effect for indapamide (0.3 mg/kg/day) characterized by a reduction in the number of cell layers (NCL; 10.5 +/- 1.8 vs. 18.0 +/- 2.9; p < 0.05) and in the intima/media area ratio (I/M; 17.5 +/- 4.5 vs. 42.7 +/- 7.0%; p < 0.01). Indapamide appeared to be more active than the reference drug flunarizine (NCL = 14.2 +/- 2.5, N.S.; I/M = 24.5 +/- 4.3, p < 0.05). The maximum effect occurred at the lowest dose tested (0.3 mg/kg/day). The reason for the loss of antiatherogenic activity of indapamide at higher doses is discussed. Hydrochlorothiazide did not show any effect on the formation of the atheromatous plaque.

Animals↗
PubMedDate not supplied

[Indapamide decreases the sensitivity of the rat tail artery to sympathetic actions and the administration of an alpha 2-adrenoreceptor agonist].

Indapamide was studied for effects on the constrictor responses of the isolated rat tail artery by using the method of "ex vivo" tail artery perfusion with blood from the awake donor rat. In acute experiments, indapamide, 3 mg/kg i. v., significantly decreased the magnitude of the electrical stimulation-induced constrictor responses of the rat tail artery. They were 77.5% (constrictor responses as % of the initial level of perfusion pressure) before indapamide injection and 37.2 and 30.2% at min 30 and 90 min after indapamide injection, respectively. In chronic experiments (15-day treatment with oral indapamide) there was a significant decrease in constrictor responses to alpha 2-agonist injected.

Adrenergic alpha-Agonists↗
PubMed1994

[Antihypertensive action of indapamide in hypertension of chronic renal failure].

Indapamide, a molecule with moderate diuretic effect, is an efficient antihypertensive drug. Blood pressure control is mostly explained by a direct action on peripheral vascular resistance. This action on peripheral resistances, as opposed to that on sodium balance, has rarely been indisputably substantiated. In order to dissociate its diuretic effect from its activity on peripheral resistances, we undertook a study on the efficacy of adding indapamide to the antihypertensive regimen of 12 patients suffering from chronic renal failure complicated by hypertension, and in whom control of high blood pressure had not been achieved with one to four antihypertensive drugs, plus furesemide in case of overhydration. Renal insufficiency was defined by serum creatinine levels of (m +/- SD) 271 +/- 171 mumol/l and a glomerular filtration rate of 36.7 +/- 18.6 ml/min. Before indapamide was introduced, blood pressure was 172.4 +/- 23.1 mmHg/109.6 +/- 9.55 mmHg. After 1 to 6 months of treatment, blood pressure was normalised. Systolic BP was 141.6 +/- 19 mmHg (p < 0.001) and diastolic BP was 89.7 +/- 8.6 mmHg (p < 0.001). Absence of diuretic effect and/or of modification of water and electrolytes was verified by the stability of body weight and serum electrolytes. At end point, body weight, electrolytes and renal function were unchanged. This study confirms that indapamide exerts an antihypertensive effect by lowering peripheral vascular resistances and not by diminishing the volume of extracellular fluid. Indapamide can be listed among antihypertensive agents that are advisable in the treatment of high blood pressure in patients with chronic renal insufficiency. Its antihypertensive effect in such patients is independent of any natriuretic action.

Ambulatory Care↗
PubMed1998

[Efficacy and safety of indapamide 1.5 mg sustained release coated tablets in the therapy of arterial hypertension].

OBJECTIVE: In line with international recommendations concerning the need to decrease the doses of antihypertensives, a low dose form (1.5 mg) of indapamide, sustained release coated tablet (SR), has been developed in order to optimize the efficacy-safety ratio while maintaining a once daily dosage. The objective of this study was to evaluate the benefit obtained by reviewing the results of two clinical trials conducted according to a similar methodology. PATIENTS AND METHODS: European randomized double-blind trials were conducted in a total of 690 hypertensive patients. The first trial was conducted in 285 patients treated for 2 months and the second trial was conducted in 405 patients treated for 3 months. The second study was extended to 9 months under open-label conditions in order to obtain a follow-up of one year with clinical and ambulatory blood pressure monitoring. The average patient characteristics on inclusion were, in the two studies: age: 53 and 57 years, 44% and 57% of men, diastolic blood pressure (DRP): 100.6 and 102.5 mmHg, systolic blood pressure (SBP): 161.0 and 164.5 mmHg. RESULTS: The first dose-ranging study demonstrated the antihypertensive efficacy of indapamide 1.5 mg SR; the study second confirmed the equivalent efficacy with the 2.5 mg immediate release form of indapamide and a greater than 50% reduction of the number of patients presenting a serum potassium less than 3.4 mmol/l. The long-term study verified the absence of therapeutic escape. Clinical safety data assessed the absence of effects of indapamide on carbohydrate and lipid metabolism. CONCLUSION: Indapamide 1.5 mg sustained release coated tablet presents an optimized antihypertensive efficacy/safety ratio in line with international recommendations concerning the use of low-dose antihypertensives and diuretics as first-line treatment for hypertension.

Antihypertensive Agents↗
PubMed1975

A double-blind study in hypertensive patients of an original new compound, indapamide.

In a double-bind crossover study in 18 patients with essential hypertension, the hypotensive activity of 5 mg. indapamide daily was compared with 40 mg. frusemide daily over a period of 4 months after an initial 15 days on placebo. The overall clinical assessment showed satisfactory blood pressure control in 72% of patients receiving indapamide compared with 57% on frusemide. The weight of patients on active therapy dropped significantly with both products, but to a greater extent with indapamide. Indapamide was well-tolerated by all 18 patients; 3 patients on frusemide developed side-effects. The results of blood chemistry investigations are discussed. Variations in potassium levels during indapamide therapy were modest and did not warrant the use of potassium supplements.

Adult↗
PubMed1986

Indapamide. Effects on apoprotein, lipoprotein, and glucoregulation in ambulatory diabetic patients.

We evaluated the long-term effects of indapamide, a non-thiazide diuretic, on blood pressure, glucoregulation, free insulin and C-peptide levels, and lipoprotein and apoprotein metabolism in 13 hypertensive diabetic patients for 24 weeks. Indapamide significantly reduced both systolic and diastolic blood pressure by 15% and 17%, respectively. Both mean fasting serum glucose and integrated glucose responses after oral glucose load (75 g) were significantly higher during indapamide therapy than at week 0. The mean fasting and stimulated C-peptide responses were significantly increased despite worsening glucose control. At the end of 24 weeks, mean glycosylated hemoglobin level had increased significantly. Indapamide caused a slight but insignificant rise in the total triglyceride, cholesterol, and low-density lipoprotein cholesterol levels, while the high-density lipoprotein cholesterol level decreased. In addition, the apoprotein A-1 concentrations remained unchanged while the apoprotein B-100 level decreased. Apart from hypokalemia (less than 3.5 mEq/L [less than 3.5 mmol/L]) in three patients that required oral potassium supplementation, biochemical changes were of no clinical consequence.

Adult↗
PubMedDate not supplied

The disposition of 14C-indapamide in man.

The metabolism of 14C-indapamide labeled in the indoline ring was determined after a single oral administration of a solution (4.99 mg, 90.47 microCi) to four fasted adult male volunteers. 14C-Indapamide was rapidly absorbed, and peak blood concentrations of radioactivity occurred by 0.5 hour in three subjects and at 2 hours in one subject. The mean elimination half-lives of total radioactivity were 27.0 hours in blood and 24.5 hours in plasma. The concentration of total radioactivity in blood was 5.7 times greater than in plasma, indicating extensive binding to red blood cells. Unchanged drug, as analyzed in one subject, reached a peak concentration by 0.5 hour, and had a blood half-life of 15.8 hours. Radioactivity was primarily excreted in the urine, and more than 50 per cent of the administered radioactivity was eliminated by this route in 48 hours. By eight days, 92.8 per cent of the radioactivity was recovered, with 70.3 per cent in the urine and 22.5 per cent in the feces. 14C-Indapamide was shown to be extensively metabolized, with only 7.3 per cent of the dose excreted as unchanged drug in the urine. Systemic and renal clearances of total radioactivity were 12.8 +/- 1.3 and 8.6 +/- 0.8 ml/min, respectively, while the renal clearance of unchanged indapamide, determined for one subject, was substantially lower (1.71 ml/min).

Adult↗
PubMed1981

Semiautomated assay for indapamide in biological fluids.

A sensitive fluorescence procedure for the determination of indapamide in plasma and whole blood was developed. The procedure requires preextraction of the biological sample followed by continuous-flow analysis. The assay is sensitive to indapamide levels of 25 ng/ml in plasma and blood. A linear response from 25 to 200 ng/ml is observed. The procedure also can be used to measure urinary levels of indapamide. The assay has been used to obtain whole blood and plasma level curves from subjects receiving 2.5 mg of indapamide.

Autoanalysis↗
PubMed1984

Once daily indapamide in the treatment of the elderly and young hypertensive.

Nine elderly and 11 young hypertensives underwent continuous ambulatory monitoring of blood pressure (BP), assessment of cardiovascular reflexes and M-mode echocardiography as hospital in-patients prior to treatment with once-daily indapamide (2.5 mg). They were followed as out-patients for 4 months during which time casual BP was measured at monthly intervals. The patients were then readmitted to hospital and studied using the same protocol under similar standardised conditions. The results showed that indapamide reduced casual and ambulatory BP in both young and elderly although the most marked effect was seen on systolic BP. Assessment of cardiovascular reflexes indicates that at least part of the hypotensive action of indapamide is due to a diuretic effect. Treatment with indapamide has comparable results on both young and elderly.

Adolescent↗
PubMed1983

Clinical efficacy and safety of indapamide in the treatment of edema.

Whether edema is caused by "overflow" or "underfill," the excess retention of salt and water is common to virtually all forms. The use of natriuretic agents has been shown to be effective in most cases of edema. The present study compares the efficacy of a new long-acting indoline compound, indapamide, with that of hydrochlorothiazide, both given once daily, in the treatment of edema. This double-blind study was conducted in 17 centers. Edema was evaluated by weight change and pitting of the lower extremities. Indapamide was given in doses of 2.5, 5.0, and 10.0 mg and was compared with 100 mg of hydrochlorothiazide. Active treatment was continued up to 12 weeks. Weight change efficacy evaluation was done on 219 patients, and efficacy analysis for pitting edema was done on 214 patients. Of the 219 subjects, 90 were men and 129 were women. Mean age was 57.4 years, and mean body weight was 88.5 kg. By the end of 2 weeks of active treatment, the percentages of patients with no edema were 26%, 44%, and 31% for the indapamide groups (2.5, 5.0, and 10.0 mg), respectively, and 40% for the hydrochlorothiazide group (100 mg). Early response to treatment as measured by weight loss was demonstrated by all patients in the study regardless of treatment group. Hypokalemia was the most frequently reported adverse reaction. Other adverse reactions were infrequent, with no significant difference among the treatment groups. This study concluded that indapamide in once-daily oral doses of 2.5, 5.0, or 10.0 mg was as safe and effective as a once-daily 100 mg dose of hydrochlorothiazide for the treatment of 219 patients with edema from various causes.

Body Weight↗
PubMed1983

Long-term experience with indapamide.

Indapamide, 2.5 mg administered once daily for periods up to 36 months, was found to be safe and effective for the long-term control of mild to moderate hypertension. The effects of hydrochlorothiazide, 50 mg, and indapamide, 2.5 mg, were studied in two randomized, double-blind, multicenter trials. Data from the two multicenter trials (20 study sites) were pooled for purposes of comparison. Significant reductions in systolic and diastolic blood pressure, with patients in both supine and standing positions, occurred in both groups within the first 8 weeks of treatment. This effect was maintained throughout the active treatment period. Success, as determined by the therapeutic success rate (percentage of patients with decreases of standing phase V diastolic blood pressure of at least 10 mm Hg or to below 90 mm Hg), occurred in 53% of the patients given hydrochlorothiazide and in 56% of the indapamide-treated patients. During the study period, the nature, frequency, and severity of adverse reactions were similar for both groups. There was no clinically significant difference between the treatment groups for the laboratory assessments. Patients who completed the multicenter trials were eligible for participation in an ongoing long-term extension study of the safety of indapamide. Data are available for periods up to 36 months and demonstrate neither augmentation of clinical or laboratory adverse effects nor any potentially harmful indicators that could be attributed to prolonged treatment.

Adult↗
PubMed1990

Effects of indapamide on left ventricular mass and function in systemic hypertension with left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) is frequently associated with hypertension and constitutes a major cardiovascular risk factor, the reduction of which should be considered when initiating antihypertensive therapy. To assess the effects of indapamide on LVH, 18 hypertensive patients were included in the study (11 men and 7 women, age 53.6 +/- 2.9 years, mean +/- standard deviation) whose supine diastolic blood pressure was greater than 95 mm Hg without (n = 11) or with (n = 7:6 beta blockers, 1 calcium antagonist) antihypertensive therapy. All presented with LVH, echocardiographically defined by a left ventricular mass index greater than 110 g/m2. After a 2-week preinclusion period, all patients received indapamide, 2.5 mg/day, for a period of 6 months. Physical examination including blood pressure measurement was performed on selection (M-1/2), before (M0), and after 1 (M1), 3 (M3) and 6 (M6) months of indapamide treatment, and echocardiography was performed at M0 and M6. Quality of life was evaluated by means of questionnaires completed by the patient and the physician, and a visual analog scale was completed by the patient at M-1/2, M0 and M6. All clinical parameters remained stable during the 2-week preinclusion period. Indapamide administration induced a highly significant reduction in both supine systolic and diastolic blood pressures from 173.9 +/- 2.9/100.5 +/- 1.2 mm Hg at M0 to 150.9 +/- 1.9/90.5 +/- 1.3 mm Hg at M1 (p less than 0.001), and 145.0 +/- 1.7/86.0 +/- 1.5 mm Hg at M6 (p less than 0.001). Similar favorable effects were observed in the upright position.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1979

Action of indapamide on excitation-contraction coupling in vascular smooth muscle.

The effects of indapamide on electrophysiological and mechanical parameters of longitudinal smooth muscle strips isolated from mammalian portal vein were studied by means of a double sucrose gap method associated with a photoelectric device for recording contraction. Indapamide (10(-4) M) reduced both the amplitude of the action potential and the contraction. The calcium inward current decreased and consequently the phasic contraction was also reduced. The potassium outward current was diminished while the tonic contraction was not modified significantly. The depressant nature of the indapamide response could counterbalance the stimulating action of angiotensin II but not that of noradrenaline. The results suggest that indapamide acts primarily on the plasma membrane of vascular smooth muscle by reducing the transmembrane calcium current, although a secondary decrease in the intracellular bound calcium could not be completely excluded.

Action Potentials↗
PubMed1981

Compared effects of indapamide, hydrochlorothiazide and chlorthalidone on electrical and mechanical activities in vascular smooth muscle.

The effects of indapamide, hydrochlorothiazide and chlorthalidone were studied on isometric contractions, calcium contractures (in depolarized preparations) and membrane potentials in isolated longitudinal strips from rat portal veins. Indapamide inhibited all three responses more potently than did current diuretics. The effects of hydrochlorothiazide and chlorthalidone appeared at concentrations at which indapamide reduced electrical and mechanical activity by more than 50%. These results confirmed that the depressing action of indapamide on vascular smooth muscle was exerted through a reduction in the transmembrane calcium influx.

Animals↗
PubMed1993

High-performance liquid chromatographic method for the determination of indapamide in human whole blood.

A sensitive, accurate, and reproducible high-performance liquid chromatographic procedure for the analysis of indapamide in human whole blood is reported. After a single-step liquid-liquid extraction at pH 6.6 using diethyl ether, indapamide was eluted from a Nucleosil C18 5-microns column with 80 mM ammonium acetate, pH 3.5-acetonitrile-2-propanol (65:30:5, v/v/v). The peak height versus whole blood concentration was linear over the range 10.0-500 ng/ml using ultraviolet detection. The mean absolute recovery of indapamide using the described assay was 87.4%. The inter- and intra-day accuracy and precision were within 9.6% of the actual values for all concentrations investigated. Furthermore, this procedure was applied to the analysis of whole blood samples from healthy subjects receiving a single 2.5-mg oral dose of indapamide.

Chromatography, High Pressure Liquid↗