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PubMed1986

Effects of furosemide and indapamide upon pancreatic insulin and somatostatin secretion in vitro.

Antihypertensive treatment with furosemide and indapamide may eventually cause impairment of glucose metabolism. To study if this was due to a direct effect on the endocrine pancreas, we examined the effects of furosemide and indapamide on the release of insulin and somatostatin from the isolated perfused pancreas of normal dogs. Furosemide at concentrations ranging between 1-30 micrograms/ml inhibited insulin in a dose-dependent manner (2p less than 0.01) whereas the somatostatin secretion was left unchanged. Also the infusion of indapamide at doses ranging between 0.05-1 micrograms/ml subdued B-cell secretion at the two highest concentrations of 0.5 (by 15 +/- 2%, p less than 0.01) and 1 microgram/ml (by 22 +/- 5%, p less than 0.02) while pancreatic D-cell secretion did not alter. The results suggest, that furosemide and indapamide possess the ability to directly inhibit insulin secretion. Whether this effect is of clinical importance for the diminution in glucose tolerance observed during therapy remains, however, uncertain.

Animals↗
PubMed1986

Effect of indapamide on atrial natriuretic polypeptide receptor in spontaneously hypertensive rat kidney.

The effect of a hypotensive state on atrial natriuretic polypeptide (ANP) receptors of the kidney treated by indapamide was investigated in spontaneously hypertensive rats (SHRs). SHRs aged 12 weeks were injected intraperitoneally with indapamide (10mg/kg/day) for 10 days and an ANP radiolabeled receptor assay (RRA) was done on the 11th day. The systolic blood pressure of SHRs injected with indapamide (IDP group) was statistically lower than that of SHRs injected with 2% gum Arabic solution (control group). Concerning the RRA of ANP in the SHR kidney, high affinity and low capacity binding sites were observed in the IDP group (Kd = 0.220 +/- 0.059 nM, Bmax = 6.10 +/- 2.36 fmol/100 micrograms) compared with the control group (Kd = 0.401 +/- 0.147 nM, Bmax = 9.96 +/- 2.50 fmol/100 micrograms). These finding suggested that the hypotensive state induced by treatment with indapamide may change the ANP receptor in kidneys of a SHR.

Animals↗
PubMed1988

Effects of indapamide on the quality of life of hypertensive patients.

This study analyzed the variation in the parameters characterizing the quality of life and well-being of hypertensive patients treated with indapamide. Thirty patients (10 men and 20 women; mean age, 52.5 +/- 2.1 years, SEM) were selected after a three-week observation period during which patients received placebo. They all had essential hypertension, defined as a diastolic blood pressure between 95 and 120 mm Hg. After the three-week placebo treatment period, indapamide was prescribed as single-agent therapy at a dose of one tablet per day (2.5 mg) for three months. The quality of life and the feeling of well-being of the treated subjects were analyzed on the basis of two self-assessment scales completed by patients and on the responses to a clinical observation scale completed during the consultation by the doctor. The decrease in blood pressure was significant (p less than 0.01) by the first month of treatment and the blood pressure was controlled (diastolic blood pressure less than 90 mm Hg) in 79.3 percent of patients by the third month. Statistical analysis of the modifications in the different scores demonstrated a significant improvement between the start and the end of the indapamide treatment period for the three types of scales (p less than 0.01). Analysis of the results also confirmed the homogeneous and significant concordance between the improvement in the responses to the doctor and patient scales. These results on the improvement in quality of life and well-being observed with indapamide demonstrate the importance of taking these aspects into consideration in the drug treatment for permanent essential hypertension.

Adult↗
PubMed1984

Indapamide, a new antihypertensive/diuretic agent, in the treatment of patients with edema.

A multicenter, double-blind, parallel-group study of 219 patients with pitting edema of various causes was undertaken to determine the efficacy and safety of indapamide, administered orally (PO) in a 2.5-, 5-, or 10-mg once-daily dose, as compared with hydrochlorothiazide, administered PO in a 100-mg once-daily dose. Efficacy was evaluated by determining each patient's weight and degree of pitting edema periodically during 12 weeks of active treatment. Lessening of edema was measured by changes in the depth of pitting in the pretibial area, ten to 14 inches below the patella. The depth of pitting was assigned an arbitrary number between 0 and 4, with 0 equivalent to no edema and 4 equivalent to more than 6 mm of pitting edema. After one week of treatment, the mean reduction of pitting edema from baseline, using the 0 to 4 scale, was 1.6 (30%) in both the indapamide (mean of the three groups) and hydrochlorothiazide groups. There were no significant differences among the three dosage levels of indapamide. After 12 weeks of treatment the mean decrease from baseline was 1.8 (34%), indicating a stable reduction of edema. The mean weight loss at one week was 2.5 kg for the three indapamide groups and 2.6 kg for the hydrochlorothiazide group; this loss was maintained for the 12 weeks of the study. The mean decreases in weight and pitting edema were clinically and statistically significant (P less than 0.05) for both medications.

Antihypertensive Agents↗
PubMed1981

Indapamide in a single daily dose in the treatment of hypertension. A multicentre trial in private practice.

In a multicentre trial a single daily oral dose of indapamide 2.5 mg (Natrilix; Servier) was prescribed to 387 hypertensive patients by their general practitioners for a period of 12 weeks, the common protocol permitting adjuvant therapy where necessary. Excellent control was achieved in indapamide alone and in 51.2% of 123 patients with more severe hypertension who were treated with indapamide combined with other hypotensive agents. Non-limiting side-effects occurred in 0.03% of patients receiving indapamide alone. The drug is considered a safe and effective agent for the treatment of mild-to-moderate hypertension (diastolic blood pressure between 90 and 129 mmHg in private practice.

Adult↗
PubMed1982

Indapamide in hypertension: a study in general practice of new or previously poorly controlled patients.

A multi-centre general practitioner study was carried out in 2497 hypertensive patients. 81% of whom were already being treated for their condition, to assess the antihypertensive activity and tolerance of indapamide (2.5 mg/day in a single dose) when given in conjunction with or as replacement for existing therapy, if any. The results showed that, over a 3-month period, indapamide produced a gradual reduction in blood pressure (mean decrease of 24/14 mmHg) and there was a direct correlation between the initial diastolic pressure and the observed reduction. Side-effects with indapamide therapy were relatively few and mild, the most frequently reported being nausea, dizziness and headache. There were no consistent changes in any of the haematological or biochemical parameters monitored. An increase was noted in subjective well-being, measured by a visual analogue scale. Analysis of the results in 772 of the patients who were aged over 65 years showed that the response to and tolerance of indapamide was similar to that in younger patients.

Aged↗
PubMed1993

Ultrastructural basis of the free-radical scavenging effect of indapamide in experimental myocardial ischemia and reperfusion.

Reperfusion of acutely ischemic cardiac tissue is associated with several characteristic pathophysiological changes that are generally referred to as "reperfusion injury." It has been hypothesized that some of these changes are mediated by oxygen-derived free radicals. Indapamide, a nonthiazide diuretic, has been shown to exert free-radical scavenging properties comparable to that of alpha-tocopherol. The purpose of the present work was to investigate whether indapamide (IDP) may limit ultrastructural signs of reperfusion injury in an experimental model of myocardial ischemia and reperfusion in isolated rat hearts. Rats received a chronic oral administration of IDP (7 days at 3 mg/kg body weight/day) before excision of the heart. IDP was also added to the perfusion fluid at a final concentration of 10(-4) M. Isolated hearts were perfused under control conditions for 20 min and then submitted to 15 min of global no-flow ischemia, before being reperfused for 15 min. Hearts were fixed by glutaraldehyde perfusion fixation and left ventricular ultrastructure was studied on ultra-thin sections by electron microscopy. Micrographs were taken following a random procedure to obtain a representative overview of the whole section. In the untreated group, marked ultrastructural alterations were observed including contraction bands, disrupted membranes, and swollen mitochondria. In the indapamide-treated group, the degree of morphological injury was significantly lessened. It is concluded that indapamide protects the ultrastructure of ventricular myocytes against reperfusion injury. This effect might be related to the oxygen free-radical scavenging property of the drug.

Animals↗
PubMed1994

[Clinical trial of indapamide in the management of central diabetes insipidus].

To investigate antidiuretic effect of indapamide, ten patients with central diabetes insipidus (CDI) were observed with the treatment of 2.5-7.5 mg of indapamide per day. After the third day of therapy, their mean daily urine output reduced by about 50%, and urine osmolality increased 1.36 times. No further change was seen in urine volume and urine osmolality on the sixth day of treatment. This antidiuretic effect was similar to that of 50-75 mg dihydrochlorothiazide per day. No adverse reaction was observed in blood pressure and serum potassium concentration during indapamide therapy. These data suggest that indapamide may be a new drug in the management of CDI.

Adolescent↗
PubMed1994

[Hypertension and well-being: a study with indapamide].

STUDY OBJECTIVE: Evaluate the clinical efficacy and quality of life of indapamide in patients with mild and moderate arterial systemic hypertension under indapamide. DESIGN: Open prospective design. SETTING: Outpatient clinics of the Instituto Nacional de Cardiologia Preventiva in Lisbon. PATIENTS: Thirty-two patients whose supine diastolic blood pressure was between 95 ans 115 mmHg without known secondary hypertension, unstable diabetes, cardiac, renal or hepatic failure, hypokalemia, coronary artery disease or stroke in the previous year. INTERVENTION: After a two week wash-out and four week placebo periods, indapamide has been given in a single daily dose of 2.5 mg at breakfast during 12 weeks. MEASUREMENTS AND MAIN RESULTS: The mean systolic/diastolic blood pressures was reduced from 155.7/103.7 to 138.6/86.1 mmHg (p < 0.0001). The mean standing systolic/diastolic blood pressure lowered from 160.2/103.7 to 141.6/85.9 mmHg (p < 0.0001). The questionnaires on quality of life and the analogic visual scale showed a progressive and significant improvement in general well-being. In the patient questionnaire the percentage of improvement was 80% (16/20 items) namely asthenia, headache, attention, dizziness, tinnitus and visual disturbance. In the physician questionnaire all the items improved. Biochemical acceptability was characterized by the stability of sodium, chlorine, glucose, creatinine, urea, cholesterol, triglycerides, uric acid and slight decrease in potassium from 4.38 to 4.14 mmol/l (p < 0.01) ranging in normal values. CONCLUSIONS: These results confirm the clinical efficacy of indapamide and its beneficial effects on quality of life in patients with mild and moderate hypertension when administered in monotherapy.

Adult↗
PubMed2003

Evaluation of the efficacy and tolerability of the combination delapril plus indapamide in the treatment of mild to moderate essential hypertension: a randomised, multicentre, controlled study.

The aim of the study was to evaluate efficacy and tolerability of two different fixed combinations of an angiotensin-converting enzyme inhibitor and a diuretic: delapril+indapamide (D+I) and captopril+hydrochlorothiazide (C+H) administered for 6 months to patients with mild to moderate essential hypertension. In all, 96 centres participated in this randomised, parallel groups, controlled study. A total of 829 patients with uncomplicated mild to moderate hypertension were randomised, and 790 were eligible for the analysis of efficacy (intention to treat). Patients of both sexes, aged 18-75 years, newly diagnosed or untreated during the last month were included in the study if their diastolic blood pressure (DBP) was > or =95 and < or =114 mmHg. The starting doses of the drugs were delapril 30 mg+indapamide 1.25 mg tablets o.d. or captopril 50 mg+hydrolchlorothiazide 15 mg tablets o.d. After a 1-month treatment period, nonresponders (DBP >90 mmHg, or decrease in DBP <10 mmHg) had the daily dose increased to either delapril 30 mg+indapamide 2.5 mg or captopril 50 mg+hydrochlorothiazide 25 mg tablets for a further 5 months. The primary assessment of antihypertensive efficacy was the percentage of patients who responded after a 6-month drug treatment. The responder rates were 72.6% with D+I and 62.9% with C+H (P=0.004 between treatments) after 60 days of treatment, and 92.6% in the D+I and 85.2% in the C+H (P<0.001 between treatments) at the end of the treatment period. The final value of systolic blood pressure was 134.5+/-13.1 mmHg with D+I and 138.3+/-14.0 mmHg with C+H (P<0.001 between treatments). At the final visit, DBP was 84.57+/-7.0 mmHg in the D+I group and 85.57+/-8.0 mmHg in the control group (P=0.017 between treatments). In all, 11 patients in the D+I group and 19 patients in the C+H group were withdrawn from the study because of adverse events. In all, 30 patients (7.6%) with D+I and 32 patients (8.1%) with C+H experienced adverse events. In conclusion, D+I was more effective than C+H in terms of overall reduction in blood pressure and response rate. Greater efficacy was obtained without any increase in adverse effects, since both treatments were equally well tolerated.

Adolescent↗
PubMed1988

Serum binding of indapamide in health and disease: primary role of alpha 1-acid glycoprotein.

The serum concentrations of alpha-1-acid glycoprotein (AAG), albumin (HSA), and non-esterified fatty acids (NEFA), and the serum binding of indapamide were measured in four groups of individuals: control (healthy) subjects (N = 24), patients with inflammatory syndrome (N = 28), with hepatic (N = 20) and renal (N = 27) insufficiency. Indapamide serum binding was increased in patients with inflammatory syndrome (82.2 +/- 3.4%, P less than .001), decreased in patients with hepatic insufficiency (72.3 +/- 5.9%, P less than .001) and unchanged in patients with renal insufficiency (77.7 +/- 2.8%) as compared with controls (78.2 +/- 3.1%). A multivariate analysis indicated that these changes were mainly related to concomitant changes in AAG concentration (that explained 63% of intersubject variability in bound/free binding ratio), and to a lesser extent to HSA (that explained only 4% of the variability in the binding). These data show that the free fraction of the acidic drug indapamide in serum is affected by pathologic conditions in which changes in AAG concentration occur and that, unexpectedly, HSA plays a negligible role in the binding.

Adolescent↗
PubMed1990

Biochemical, endocrine, and mineral effects of indapamide in black women.

Black women with established essential hypertension, without renal insufficiency or diabetes mellitus, were withdrawn from their usual antihypertensive therapy for 2-3 weeks prior to entry into a study to evaluate pertinent biochemical and mineral effects of indapamide treatment. Twenty patients with a sitting diastolic blood pressure greater than 90 mm Hg had baseline measurements of plasma total cholesterol, HDL cholesterol, triglycerides, glucose, uric acid, potassium, magnesium, calcium, selenium, renin, norepinephrine, whole blood ionized calcium, and glycosylated hemoglobin. Low-density lipoprotein (LDL) cholesterol was calculated by the Friedewald equation. The patients were placed on a fixed daily dose of 2.5 mg indapamide. Blood pressure and blood tests were repeated at 4, 8, and 12 weeks of treatment. The systolic and diastolic blood pressure were both lowered significantly at week 12. Plasma renin activity was significantly increased. There was no significant change in norepinephrine, glucose, glycosylated hemoglobin, uric acid, ionized calcium, calcium, triglycerides, potassium, magnesium, or selenium. Total cholesterol increased with an increase in both high-density lipoprotein (HDL) and LDL cholesterol; however, these increases did not alter significantly either the total/HDL cholesterol or LDL/HDL cholesterol ratios. It is concluded that 2.5 mg of indapamide per day effectively lowers blood pressure with no significant adverse metabolic effects.

Adult↗
PubMed1980

Automated analysis of indapamide in drug-rodent food mixtures.

Indapamide, an antihypertensive agent, is an aryl sulfonamide that inhibits carbonic anhydrase in vitro but not in vivo. An assay was developed for indapamide in drug-rodent food mixtures that utilizes this inhibitory effect. Indapamide was extracted from the mixtures with methanol, and an aqueous dilution of the extract was sampled by a continuous-flow system. In the system, the drug was extracted with butanol and then back-extracted into alkali. This solution was neutralized, buffered, and mixed with bovine erythrocyte carbonic anhydrase. The substrate, p-nitrophenyl acetate, was added, the solution was incubated, and the amount of p-nitrophenol formed was measured. The assay was sensitive to 20 micrograms of indapamide/g of food, and 20 unknown samples could be analyzed per hour on the continuous-flow system. It is possible that the method could be extended to the analysis of other toxicological test substances that inhibit carbonic anhydrase in vitro.

Animal Feed↗
PubMed2005

The Na+-excreting efficacy of indapamide in combination with furosemide in massive edema.

BACKGROUND: Massive systemic edema is often observed in patients with severe nephrotic syndrome, including diabetic nephropathy. Although furosemide, a loop diuretic, is often administered to these patients, some patients do not respond to this treatment, still showing massive edema. METHODS: The efficacy of indapamide which has a thiazide-like effect on distal convoluted tubules in combination with furosemide, was evaluated in eight patients with massive edema, in regard to both Na+ excretion and diuresis. Indapamide 2 mg was administered once a day, in the morning, to patients in whom it was considered that furosemide treatment of 40-120 mg a day for 1 week was ineffective. RESULTS: Urinary Na+ excretion was markedly increased, from 83.7 +/- 82.2 mEq/day to 140.7 +/- 33.8 mEq/day after 1 week of the combination therapy compared with furosemide alone (P < 0.01); urine volume was also increased, from 1070 +/- 230 ml to 1359 +/- 296 ml after 1 week of the combination therapy (P < 0.05). In this context, body weight was significantly decreased, from 57.2 +/- 12.3 kg to 53.4 +/- 12.8 kg, after the combination therapy (P = 0.01). Indapamide in combination with furosemide was well tolerated, and no significant changes in serum levels of creatinine and potassium were observed. CONCLUSIONS: This combination therapy appears to be effective in patients with massive edema, as it increased diuresis, and achieved potent Na+ excretion.

Adult↗
PubMed1983

Clinical efficacy, safety, and pharmacokinetics of indapamide in renal impairment.

The efficacy and safety of a new diuretic-antihypertensive drug, indapamide (2.5 mg/day), were evaluated in hypertensive patients with normal renal function, in patients with various degrees of chronic renal failure, and in hypertensive patients undergoing long-term maintenance hemodialysis. The results obtained from single-blind, placebo-controlled studies indicate that indapamide is a safe and effective agent to use in lowering the blood pressure of hypertensive patients with normal renal function, those with various degrees of renal impairment, and those who are undergoing long-term maintenance hemodialysis. No significant side or toxic effects were noted in these studies. Furthermore, indapamide does not accumulate in the bloodstream of patients with renal impairment and is not dialyzable.

Aldosterone↗
PubMed1991

Regression of left ventricular hypertrophy in hypertension with indapamide.

In hypertensive patients, the development of left ventricular hypertrophy seems to increase the risk of cardiovascular death. Although some antihypertensive agents have been associated with regression in left ventricular hypertrophy, diuretics, the most widely used ones, have not. Indapamide is a new, nonthiazide diuretic and vasodilator. To test its effects on left ventricular hypertrophy, patients with essential hypertension and left ventricular hypertrophy were studied before and at the end of 6 months of therapy with 2.5 mg of indapamide daily. Candidates had to have moderate, uncontrolled essential hypertension with echocardiographically documented left ventricular hypertrophy (left ventricular mass index greater than or equal to 130 gm/m2 for men and greater than or equal to 110 gm/m2 for women). Patients with complicated hypertension or with significant cardiovascular or metabolic diseases were excluded. Patients could remain on antihypertensive drugs other than diuretics, provided doses remained stable for 3 months before entry and there was no know regression of left ventricular hypertrophy. Of 13 patients selected, 2 dropped out. The remaining 11 patients successfully completed 6 months of therapy. The average age was 56 +/- 10 years. Indapamide was associated with a significant reduction of mean systolic blood pressure from 172 to 142 mm Hg (p less than 0.001), diastolic blood pressure from 101 to 83 mm Hg (p less than 0.001), and left ventricular mass index from 146 +/- 22 to 124 +/- 22 gm/m2 (mean +/- SD) (p less than 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effects of indapamide on the mechanical properties of the arterial wall in deoxycorticosterone acetate-salt hypertensive rats.

An experimental model of "in situ" isolated carotid artery has been used to evaluate the static mechanical properties of the arterial wall in 12-week-old Wistar and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The rats were made hypertensive by left kidney removal, DOCA (50 mg) tablet implantation for 2 weeks, and saline diet (NaCl 9% solution as beverage). Normotensive control rats (n = 24) and DOCA-salt hypertensive rats (n = 24) received indapamide, 10 mg/kg, or placebo by gavage 12 hours and 1 hour before measurements were obtained. The rats were anesthetized (pentobarbital 50 mg/kg), intubated and ventilated, and a midsternal thoracotomy was performed. A first catheter was introduced into the ascending aorta through the right carotid artery. A perivascular ultrasonic flow probe was placed around the ascending aorta and allowing simultaneous recording of the phasic ascending aortic pressure and flow. Systolic and diastolic pressure, cardiac output and heart rate were directly measured. Peripheral resistance and systemic arterial compliance were calculated from hemodynamic records. After hemodynamic measurements, a segment of the left carotid artery was then isolated in vivo and its volume-pressure relationship was recorded before and 30 minutes after total abolition of the vascular muscle tone by local incubation with a potassium cyanide solution (KCN) (100 mg/liter) for pressures ranging from 50 to 175 mm Hg. The carotid compliance (CC) (microliter/mm Hg) was calculated, for every pressure step, as the slope of the volume-pressure curves. Indapamide significantly reduced the arterial pressure in hypertensive rats, and this was related to a marked decrease in total peripheral resistance. Heart rate was not modified by indapamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Twenty-four-hour blood pressure monitoring and effects of indapamide.

Twenty-four-hour blood pressure (BP) monitoring with a noninvasive device (Kontron) has been used to assess the effect of a single dose of indapamide in a group of patients with essential hypertension. Originally 23 patients were selected. Three patients withdrew from the study because of refusal to go through the second 24-hour recording. Eight of the remaining patients had to be excluded for technical reasons, which left 12 patients available for analysis. All patients received a single dose of indapamide, 2.5 mg/day. Before treatment began, a 24-hour BP control was performed, and a second one a month later (37 +/- 8 days). The age of the patients was 46 +/- 10 years. Diurnal BP (8 am to 10 pm) and heart rate were, respectively, 148 +/- 15/101 +/- 6 mmHg and 79 +/- 9 beats/min; night BP (10 pm to 8 am) was 131 +/- 15/88 +/- 7 mmHg and heart rate 71 +/- 10 beats/min. After therapy, diurnal BP was 131 +/- 15/92 +/- 7 mmHg (-15 +/- 7/-8 +/- 4: p less than 0.0001/p less than 0.0001); heart rate 82 +/- 8 beats/min (difference not significant); night BP was 115 +/- 13/80 +/- 8 mmHg (-16 +/- 11/-8 +/- 7: p less than 0.0001/p less than 0.0001) and heart rate 70 +/- 9 beats/min (difference not significant). Twenty-four-hour systolic work values were 106 +/- 15 at the beginning of the trial and 96 +/- 14 (-9.7 +/- 14; p less than 0.05) after 1 month of indapamide treatment. Variability did not change with treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗