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PubMed1996

A comparison of blood lipid and blood pressure responses during the treatment of systemic hypertension with indapamide and with thiazides.

Thiazide diuretics in high dosage adversely affect the lipid profile. The non-thiazide indoline, indapamide, appears to be free of this effect, but it is unclear whether this apparent metabolic advantage of indapamide is superior to thiazides used in low dose. Since there are no large direct comparative studies to test this distinction, I surveyed the literature and pooled the findings of all published reports giving data on lipid and blood pressure effects of thiazides in various doses and of both indapamide, 2.5 mg daily, used as monotherapy of hypertension. I found 31 reports of thiazides; 12 of them examined low-dose regimens, i.e., < or = 25 mg/day of hydrochlorothiazide or its equivalent in other thiazides. Larger doses of thiazides were tested in 19 studies (median daily dose of 50 mg, maximum dose of 112.5 mg). There were 430 subjects in the low-dose studies and 559 subjects in the high-dose regimens. There were 13 studies of indapamide, comprising 558 subjects. Regarding lipids, total cholesterol increased from baseline by 1.4% on indapamide, 3.8% on low-dose thiazides, and 6.3% on high-dose thiazides, The change from baseline was significantly greater for high-dose thiazides than for indapamide (p<0.01). Changes in high-density lipoprotein cholesterol did not differ among groups. The change in triglycerides differed among regimens, -0.5%, 10.8%, and 19.5% for indapamide, low-dose thiazides, and high-dose thiazides, respectively (p<0.01). Systolic blood pressure (SBP) decreased by 13 and 18 mm Hg on low-dose and high-dose thiazides, respectively (p<0.05 between doses). Indapamide lowered SBP by 16 mm Hg, not different from either thiazide dose. Diastolic blood pressure did not differ among groups. From these noncomparative studies, I conclude that (1) indapamide has no adverse lipid effect and lowers blood pressure equally to thiazides; (2) thiazide effects on lipids and SBP are dose-dependent; and (3) thiazides adversely affect the lipid profile even in low dose.

Antihypertensive Agents↗
PubMed2006

The impact of one or two missed doses on the duration of action of combined perindopril and indapamide.

To evaluate the persistence of the antihypertensive effect of perindopril 4 mg+indapamide 1.25 mg once daily for up to 72 h using the 'missed-dose' technique. Hypertensive patients were initially treated with perindopril 2 mg+indapamide 0.625 mg once daily. After 4 weeks, the 135 of 216 patients who still had a diastolic BP> or =85 mm Hg went on to receive perindopril 4 mg+indapamide 1.25 mg daily for a further 8 weeks. During either week 9 or 11, placebo was substituted for perindopril 4 mg+indapamide 1.25 mg on either one or two consecutive days to simulate BP changes, which might occur after one or two missed doses. A 24-h ambulatory BP recording was performed at baseline, after 9 or 11 weeks of perindopril+indapamide therapy and during the simulated missed doses, 24- 48 and 48-72 h after the administration of perindopril 4 mg+indapamide 1.25 mg. Significant (P<0.001) reductions in mean (+/-s.d.) 24-h ambulatory BP (mm Hg) during the first 24 h after perindopril 4 mg+indapamide 1.25 mg therapy versus baseline were noted for patients later randomized to the one missed dose (-15.9+/-10.5/-9.4+/-7.6) or two missed dose (-17.4+/-8.7/-10.3+/-5.1) sub-groups. A significant reduction in BP (P<0.001 versus baseline) was still present on the days when placebo was substituted for perindopril 4 mg+indapamide 1.25 mg with decreases in mean 24-h ambulatory BP from 24 to 48 h and 48 to 72 h after dosing being -11.9+/-10.1/-6.9+/-6.2 and -10.6+/-9.9/-5.8+/-5.7, respectively. Use of the 'missed-dose' technique has demonstrated a prolonged antihypertensive effect for perindopril 4 mg+indapamide 1.25 mg for up to 72 h, supporting the use of this combination as therapy for hypertension.

Antihypertensive Agents↗
PubMed1998

Use of indapamide in hospital and community clinics and its effect on plasma potassium in Chinese patients.

OBJECTIVES: To investigate the usage pattern of indapamide and other antihypertensive drugs in patients attending a community-based government outpatient clinic (GOPC) or a hospital-based specialist clinic (SC). The plasma potassium concentrations of patients receiving indapamide and other diuretics were also examined. METHOD: Prescriptions from the SC and the GOPC were reviewed and collected during January 1998. Patients' plasma potassium concentrations and the date of initiation of each medication were retrieved from the hospital computer databases at SC. An age- and sex-matched control group of patients on non-diuretic antihypertensive drugs was identified. RESULTS: A total of 1648 and 773 prescriptions were collected from the SC during a 1-week period and GOPC during a 1-month period, respectively. Approximately half (45%) of the patients received antihypertensive treatment. Indapamide was five times more frequently prescribed in GOPC than SC (84.7 vs. 17.7%, P<0.001). Calcium channel blocking agents were the commonest antihypertensive drugs used in both clinics. The mean plasma potassium concentration of patients taking indapamide was lower than that of the control group (P = 0.037). Multiple linear regression analysis showed that consumption of indapamide (P =0.002) and duration of diuretic therapy (P = 0.023) were significantly related to changes in plasma potassium concentrations [multiple regression equation for potassium level = 4.09-0.145 (thiazide = 1)-0.377 (indapamide = 1) -0.00468 (duration of diuretic therapy in months)]. CONCLUSION: Indapamide was used extensively in the community clinic and less in the hospital-based outpatient clinic. Patients receiving indapamide had a significantly lower plasma potassium concentration as compared to other diuretics or antihypertensive groups and this was predicted by a multiple linear regression model. Monitoring plasma electrolytes before initiation of indapamide treatment and at regular intervals thereafter is essential for detecting the hypokalaemia that may occur in Chinese patients.

Aged↗
PubMed1998

Low-dose antihypertensive therapy with 1.5 mg sustained-release indapamide: results of randomised double-blind controlled studies. European study group.

OBJECTIVE: In accordance with international recommendations on the need to decrease doses of antihypertensive drugs, a low-dose (1.5 mg) sustained-release (SR) formulation of indapamide was developed to optimize the drug's efficacy : safety ratio. The aim of this work was to evaluate the benefit of a low-dose diuretic by consolidating the efficacy and safety results of two clinical trials with a similar design. PATIENTS AND METHODS: Clinical data were obtained in two European randomized double-blind studies with 690 mild to moderate hypertensive patients (95 mmHg < or = supine diastolic blood pressure < or = 114 mmHg using a mercury sphygmomanometer) treated respectively for 2 and 3 months, with a mean age of 53 and 57 years, 44 and 57% males, mean supine diastolic blood pressure of 100.6 and 102.5 mmHg and mean supine systolic blood pressure of 161.0 and 164.5 mmHg. RESULTS: The first study, a dose-finding study with indapamide SR at 1.5, 2 and 2.5 mg versus placebo and the immediate-release (IR) formulation of indapamide, showed that the 1.5 mg dosage of the new indapamide formulation had an improved antihypertensive efficacy : safety ratio. The second study confirmed the equivalence of blood pressure reductions with 1.5 mg indapamide SR and 2.5 mg indapamide IR, and better acceptability with 1.5 mg indapamide SR, particularly in the number of patients with serum potassium levels < 3.4 mmol/l, which was reduced by more than 50%. The long-term efficacy of 1.5 mg indapamide SR was observed through a 9-month open-treatment follow-up to the second study. CONCLUSION: The 1.5 mg SR formulation of indapamide has an improved antihypertensive efficacy : safety ratio, which is in accordance with international recommendations for the use of low-dose antihypertensive drugs and diuretics in first-line therapy of hypertension.

Adult↗
PubMed1999

Clinical implications of indapamide sustained release 1.5 mg in hypertension.

Recent international guidelines on the detection, clinical assessment and management of patients with hypertension have highlighted a number of themes that should be incorporated into routine clinical practice. First, although antihypertensive therapy is having a major impact on reducing the incidence of coronary heart disease, cerebrovascular disease and heart failure, community surveys show that most hypertensive patients remain untreated or have suboptimal blood pressure control. Second, the guidelines have emphasised the importance of making an overall assessment of individual patients to gauge their absolute risk of a cardiovascular event; risk factors include not only blood pressure but also target organ damage, the presence of coexisting symptomatic vascular disease and the number of associated cardiovascular risk factors. Patients at the highest risk, especially those with diabetes, the elderly and patients with target organ damage, merit vigorous antihypertensive therapy, and such patients often require treatment with more than one drug to achieve target levels of blood pressure (< 135/80 mm Hg). An additional important theme in recent guidelines has been a move towards using lower dosages and therapies that provide 24-hour blood pressure control with once-daily administration. Since diuretics have been reaffirmed as evidence-based first-line therapy in a broad spectrum of patients with hypertension, especially the elderly, a new lower dosage sustained release formulation of indapamide has been developed (indapamide SR 1.5 mg). Recent multicentre European clinical trials have defined the efficacy and tolerability of indapamide SR 1.5 mg, both relative to other antihypertensive drugs and in key subgroups of patients. Indapamide SR 1.5 mg has an antihypertensive effect, maintained throughout the 24-hour administration interval, equivalent to that of immediate release indapamide 2.5 mg, but the new formulation has even less effect on circulating K+ levels. Indapamide SR 1.5 mg is at least as effective as amlodipine or hydrochlorothiazide. In patients with left ventricular hypertrophy (LVH), a comparative study of indapamide SR 1.5 mg and enalapril (the LIVE study) used a rigorous unique study design with blinded reading of echocardiograms to show that after 1 year the ACE inhibitor had no significant effect on LVH regression, whereas indapamide SR 1.5 mg produced significant reductions in left ventricular mass index. Diuretic-based therapy for hypertension has been reaffirmed in international guidelines as effective first-line therapy, especially in the elderly and patients with LVH. Indapamide SR 1.5 mg shows an improved efficacy-tolerability profile, with impressive 24-hour effects on blood pressure, important ancillary properties with regard to LVH and cardiovascular protection.

Age Factors↗
PubMed1988

Hypertension in elderly patients. A comparative study between indapamide and hydrochlorothiazide.

Diuretic therapy is still regarded as the first-step approach in elderly patients with benign or moderate arterial hypertension. Traditional preparations such as thiazides, or potassium-sparing agents, are not devoid of significant side effects, however. Indapamide, a nonthiazide diuretic, has been shown to reduce blood pressure at low doses, in several clinical reports. In the present study, the effect of indapamide (2.5 mg per day) was compared with that of hydrochlorothiazide (50 mg per day) on blood pressure and serum chemistry of 47 elderly hypertensive patients (ages 65 to 91). After a six-week placebo-treatment period, patients were randomly assigned to receive either indapamide or hydrochlorothiazide. At that moment, blood pressure of patients in the supine position averaged 185 +/- 2/107 +/- 2, and 181 +/- 3/102 +/- 2 mm Hg, in the indapamide and hydrochlorothiazide groups, respectively. After 48 weeks of therapy, blood pressure was 162 +/- 3/89 +/- 2 and 170 +/- 2/94 +/- 2 mm Hg in the same groups, respectively. Serum sodium levels remained unchanged in indapamide-treated patients, but decreased progressively from 141 +/- 1 to 134 +/- 1 meq/liter in hydrochlorothiazide-treated patients. Serum potassium levels decreased from 4.50 +/- 0.12 to 4.04 +/- 0.10 meq/liter in indapamide-treated patients, whereas in the patients receiving hydrochlorothiazide, kalemia decreased from 4.23 +/- 0.09 to 3.33 +/- 0.01 meq/liter. Finally, serum uric acid levels did not increase significantly in patients receiving indapamide, whereas it rose from 6.5 +/- 0.4 to 8.7 +/- 0.3 mg/dl in patients treated with hydrochlorothiazide. In conclusion, indapamide resulted in a better control of systolic and diastolic blood pressure in this group of elderly hypertensive patients. In addition, the effect of each drug on blood chemistry differed markedly: indapamide failed to alter significantly the serum ionic composition, whereas hydrochlorothiazide was associated with both hyponatremia and hypokalemia.

Aged↗
PubMed1982

[Antihypertensive and diuretic effects of indapamide in normotensive and hypertensive rats (author's transl)].

Antihypertensive and diuretic actions of indapamide (SE-1520) were investigated in rats and compared with those of trichlormethiazide (TCMT). In normotensive rats, indapamide in a dose of 100 mg/kg p.o. did not show a significant effect on the blood pressure. In DOCA-saline and uni-nephrectomized DOCA-saline hypertensive rats, indapamide above 1 mg/kg and TCMT above 3 mg/kg with single oral or repetitive administration for 2 weeks reduced the blood pressure level. In spontaneously hypertensive rats (SHR), both indapamide and TCMT lowered the blood pressure with single doses above 10 mg/kg or repetitive doses above 3 and 10 mg/kg, respectively. In the diuretic test using normal rats, indapamide in doses ranging from 0.1 to 30 mg/kg increased urine volume and urinary electrolyte excretion. TCMT showed a more potent diuretic action at a lower dose level. In SHR, indapamide and TCMT produced a greater urine volume and electrolytes excretion. Indapamide inhibited the carbonic anhydrase activity and the potency was about 1/25 of that of acetazolamide in vitro. The antihypertensive activity of indapamide was more potent than that of TCMT and the reverse order to that of their diuretic potencies. It is suggested that the mechanism of antihypertensive effect of indapamide is different from that of TCMT.

Animals↗
PubMed1991

Indapamide potentiates the endothelium-dependent production of cyclic guanosine monophosphate by bradykinin in the canine femoral artery.

Indapamide is a sulfonamide diuretic agent that has antihypertensive properties. In the canine femoral artery, indomethacin reduces the endothelium-dependent relaxation induced by bradykinin, and indapamide restores the response. The aim of this study was to determine whether indapamide affects the release or the effects of endothelium-derived nitric oxide and prostanoids. The effect of indapamide on the production of endothelium-derived nitric oxide and prostacyclin was assessed indirectly by the measurement of the tissue content of cyclic guanosine monophosphate (GMP) and the accumulation of 6-keto-prostaglandin F1 alpha in the incubation medium, respectively. Indapamide did not affect the basal production of either cyclic GMP, cyclic adenosine monophosphate (AMP), or 6-keto-prostaglandin F1 alpha in the presence or absence of indomethacin. Indomethacin decreased the production of cyclic AMP and the release of 6-keto-prostaglandin F1 alpha induced by bradykinin, and this was unaffected by indapamide. Indapamide enhanced the bradykinin-stimulated production of cyclic GMP in the presence of indomethacin and did not affect that evoked by 3 morpholino-sydnonimine, an exogenous donor of nitric oxide. Indomethacin had no significant effect on the production of cyclic GMP stimulated by either bradykinin or 3 morpholino-sydnonimine. These studies demonstrate that the potentiation by indapamide of the relaxation evoked by bradykinin is associated with an enhanced production of cyclic GMP in the presence of indomethacin, which suggests that the production of endothelium-derived nitric oxide is increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Possible induction of diabetes by treatment of hypertension with indapamide (with four case reports).

OBJECTIVE: To study therapy with indapamide impairing carbohydrate metabolism in essential hypertension patients and achieve earlier prevention, diagnoses and treatment of diabetes induced by indapamide. METHODS: Four cases of essential hypertension patients (1 male and 3 females) were observed through process of therapy with indapamide and laboratory investigations. RESULTS: After 4- to 14-month period of therapy with the combination of indapamide (2.5 mg/day) and fosinopril (10 mg/day) in three patients and 6-month period of monotherapy with indapamide (2.5 mg/day) in one patient, glucose levels of all patients increased and achieve criteria of diabetes diagnoses. After 3- to 13-month period of therapy without indapamide, glucose levels of all patients decreased and diabetes disappeared. CONCLUSION: Therapy with indapamide may induce diabetes in essential hypertension patients. After stopping indapamide, glucose tolerance impairing may be reversed.

Adult↗
PubMed2003

Effect of indapamide SR in the treatment of hypertensive patients with type 2 diabetes.

BACKGROUND: To evaluate the effect of the sustained-release formulation of indapamide (indapamide SR) in type 2 diabetic patients with mild-to-moderate hypertension and its possible side effects, particularly on glucose metabolism and lipid profiles. METHODS: A total of 64 patients randomly received 1.5 mg of indapamide SR or placebo once daily for 3 months. The effects were evaluated by 24-h ambulatory blood pressure monitor, fasting blood sampling for biochemistry, lipid profiles, and frequently sampled intravenous glucose tolerance test. RESULTS: The changes in standing and supine blood pressure (BP) were significant (154.7 +/- 9.4/94 +/- 2.9 mm Hg v 134.4 +/- 5.1/82.4 +/- 5 mm Hg and 155 +/- 9.8/94.6 +/- 3.6 mm Hg v 135.1 +/- 4.9/82.1 +/- 4.7 mm Hg) in the indapamide group, but not in the placebo group. According to the 24-h ambulatory blood pressure monitor reading, a significant reduction was observed in not only in the whole-day mean BP (mean systolic BP/mean diastolic BP, 149 +/- 19.3/87.6 +/- 11.3 mm Hg v 135.7 +/- 12.6/79.6 +/- 9 mm Hg) but also the whole-day mean median arterial pressure (109 +/- 12.7 mm Hg v 98.7 +/- 8.2 mm Hg) for the indapamide group, but not the placebo group. There were no changes in biochemical data including serum sodium, potassium, chloride, uric acid, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, lipid profiles, fasting blood glucose, insulin, hemoglobin Alc, and glucose metabolism parameters (insulin sensitivity, glucose effectiveness, and acute insulin response) from frequently sampled intravenous glucose tolerance test after indapamide or placebo therapy. CONCLUSIONS: Indapamide SR can significantly lower the whole-day BP in hypertensive patients with type 2 diabetes. Also, it did not alter or aggravate patients' lipid profiles, glucose metabolism, and did not exert possible side effects of hypokalemia and hyperuricemia. Therefore, monotherapy with indapamide SR should be suggested in type 2 diabetic patients with mild-to-moderate hypertension.

Aged↗
PubMed1998

Indapamide improves flow-induced dilation in hypertensive rats with a high salt intake.

OBJECTIVE: Spontaneously hypertensive rats (SHR) are sensitive to a high salt intake and we investigated the question of whether flow-induced dilation is affected by this type of diet, as flow responses are especially sensitive to small changes in extracellular sodium concentrations. METHODS: We evaluated the effects of a diuretic (indapamide, 1.5 mg/kg per day, 8 weeks) on four groups of SHR (n=42). One group was fed with a normal-salt diet (0.4%, control group, n=10), the second with a high-sodium diet (8%, n=12), the third with a high-sodium diet and indapamide (1.5 mg/kg per day, 8% salt, n=10) and the fourth group was fed with indapamide alone (1.5 mg/kg per day, n=10). The response to flow was studied in mesenteric resistance arteries (146+/-6.1 microm internal diameter, pressure 100 mmHg) cannulated in vitro in an arteriograph. RESULTS: The increase in mean arterial pressure (from 186+/-4 to 218+/-6 mmHg; P < 0.01) and heart weight: body weight ratio (3.48+/-0.09 versus 4.34+/-0.1 mg/g; P< 0.01) caused by the high salt intake was prevented by indapamide. A high salt intake significantly decreased flow-induced dilation (6+/-0.8 versus 10.7+/-1.2 microm dilation with a flow of 160 microl/min; P< 0.05), while indapamide significantly prevented the decrease in flow-induced dilation in high-salt SHR. Indapamide had no significant effect on flow-induced dilation in mesenteric resistance arteries from SHR with a normal-salt diet. CONCLUSIONS: Indapamide prevented the decrease in flow-induced dilation caused by a high-salt diet Therefore, indapamide might counteract the disturbance in sodium-sensitive flow sensor(s), through a diuretic effect.

Animals↗
PubMed2002

Dose-dependent prevention of fibrosis in aorta of salt-loaded stroke-prone spontaneously hypertensive rats by combined delapril and indapamide treatment.

Combined treatment with the angiotensin-converting enzyme (ACE) inhibitor delapril and the diuretic indapamide prevented vascular damage in vital organs of salt-loaded stroke-prone spontaneously hypertensive rats (SHRsp). Whether the changes occurring after long-term hypertension could also be modulated in large arteries was investigated. Two-month-old SHRsp were salt loaded and treated with the drug regimen until they reached 50% mortality or around midlife. In a first experiment, delapril (12 mg/kg) and indapamide (1 mg/kg) were administered daily separately or in combination. In the second dose-finding experiment, delapril (6, 3, 1.5 mg/kg) and indapamide (0.5, 0.25, 0.125 mg/kg) in decreasing dose combinations were analyzed. Ultrastructural, histomorphometric, and biochemical studies were performed on the thoracic aorta. When compared with delapril (12 mg/kg) or indapamide (1 mg/kg) administered individually for 5 months, the combination 12 + 1 mg/kg was able to prevent the increase in extracellular matrix deposition observed in other treatment groups, as assessed by histomorphometry or 4-OH-proline biochemical determination. In the second experiment, a half-dose (delapril 6 mg/kg + indapamide 0.5 mg/kg) combination was similarly effective in counteracting fibrosis, but the other doses progressively failed. In the first experiment, the combination had a stabilizing effect on hypertension and stimulated diuresis. In the second experiment, arterial blood pressure values and sodium balance were not consistently affected by the treatments that antagonized fibrosis (i.e., delapril 6 mg/kg + indapamide 0.5 mg/kg and, less efficiently, delapril 3 mg/kg + indapamide 0.25 mg/kg). These results suggest that indapamide interacts with ACE inhibitors to limit aortic fibrosis independent of any well-established mechanism.

Animals↗
PubMed1990

Radical scavengers of indapamide in prostacyclin synthesis in rat smooth muscle cell.

Indapamide, a nonthiazide diuretic, exhibits direct vasodilator action as well as natriuretic and diuretic effects. Although calcium antagonist-like activity has been addressed so far, the mechanisms for vasodilator effect are still uncertain. To understand the wide range of indapamide actions, we examined the effects of indapamide on the vascular eicosanoid generation and investigated its mechanisms by using rat vascular smooth muscle cells in culture. Indapamide uniquely increased the prostacyclin generation in the vascular smooth muscle cells in a dose-dependent manner, whereas it did not affect the vasoconstrictor thromboxane A2. Thiazide diuretics lowered the prostacyclin generation, while nonthiazide derivatives did not affect the biosynthesis. Enzymatic analysis revealed that indapamide affected neither [14C]arachidonate liberation nor prostacyclin synthase of the smooth muscle cells. Indapamide eliminated a stable free radical in a cell-free system, lowered the formation of malondialdehyde from lipid peroxides in rat brain homogenate, and reduced lipid peroxidation by the free radical generating system of xanthine-xanthine oxidase. Indeed, the scavenging action of indapamide significantly attenuated the inhibitory activity of 15-hydroperoxy-arachidonate to prostacyclin synthase activity. These results indicate that indapamide diuretic increases prostacyclin generation in the vascular smooth muscle cells possibly through antioxidant effects and that the enhanced prostacyclin generation is partly responsible for its direct vasodilator action.

Animals↗
PubMed1994

Block of IKs, the slow component of the delayed rectifier K+ current, by the diuretic agent indapamide in guinea pig myocytes.

There is a high incidence of diuretic use among patients who develop exaggerated QT prolongation and polymorphic ventricular tachycardia (torsade de pointes) during treatment with action potential-prolonging agents. Diuretic-induced hypokalemia is thought to be the usual mechanism, but a direct effect of diuretic drugs on repolarizing currents is an additional possibility. Therefore, in this study, we examined the effects of the diuretic agents chlorthalidone and indapamide on the cardiac delayed rectifier current. In guinea pig ventricular myocytes, this current is made up of two components: IKr, a rapidly activating, inwardly rectifying current blocked by most action potential-prolonging antiarrhythmics, and IKs, a slowly activating component. In this preparation, indapamide blocked outward current in a time-, voltage- and concentration-dependent fashion, whereas chlorthalidone (1 mmol/L) was without effect. The following features of the effect of indapamide strongly suggest selective block of IKs: (1) Indapamide block was significantly greater with 5000-millisecond activating pulses (-43 +/- 5% at +50 mV [100 mumol/L indapamide]) than with 225-millisecond ones (-20 +/- 5%; n = 5, P < .01), and the signature of the indapamide-sensitive current was a slowly activating delayed rectifier current. (2) The voltage dependence of indapamide block (EC50, 101 mumol/L at +50 mV and 196 mumol/L at +10 mV) was consistent with preferential block of IKs relative to IKr. (3) In the presence of indapamide, an envelope-of-tails test for IKr was satisfied. The drug-insensitive current had rectifying properties similar to those described for IKr in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1998

Effects of the diuretic agent indapamide on Na+, transient outward, and delayed rectifier currents in canine atrial myocytes.

The diuretic agent indapamide has been reported to block the slow component of the delayed rectifier K+ current (IKs) without altering the rapid component (IKr) or the inward rectifier current and has been used as a pharmacological probe for IKs; however, the effects of indapamide on Na+ (INa), L-type Ca2+ (ICa), and transient outward K+ (Ito) currents have not been determined. We applied tight-seal, whole-cell, patch-clamp techniques to assess the effects of indapamide on INa, Ito, ICa, and IKs in canine atrial myocytes. Indapamide inhibited INa, Ito, and IKs in a concentration-dependent and reversible way, without altering ICa. Block increased with depolarization, with the 50% blocking concentration (EC50) decreasing from 129 +/- 26 micromol/L (at -60 mV) to 79 +/- 17 micromol/L (at -10 mV) for INa, from 174 +/- 19 micromol/L (at + 10 mV) to 98 +/- 7 micromol/L (at +60 mV) for Ito and from 148 +/- 28 micromol/L (at +10 mV) to 86 +/- 18 micromol/L (at +60 mV) for IKs. Significant inhibition was seen at concentrations as low as 10 micromol/L for all 3 currents. In addition, indapamide effectively inhibited the ultrarapid delayed rectifier current in a voltage-independent way, with an EC50 of 138 +/- 7 micromol/L at +10 mV. Standard microelectrode experiments showed the effects of indapamide on the action potential to be consistent with the ionic actions seen. We conclude that in addition to its well-recognized IKs-blocking action, indapamide also inhibits INa and Ito effectively and with similar potency. Thus, indapamide is not a reliable pharmacological probe with which to study the specific effects of IKs blockade, and INa and Ito block may contribute to the potential profile of cardiac actions of the compound.

Action Potentials↗
PubMed1999

Galenic development and pharmacokinetic profile of indapamide sustained release 1.5 mg.

In accordance with international guidelines recommending the use of low doses of antihypertensive agents, a new formulation of indapamide--indapamide sustained release (SR)--has been developed. Indapamide has been used worldwide for many years as an immediate release (IR) formulation at a dose of 2.5 mg. The IR formulation leads to plasma peaks of indapamide immediately after administration of the tablet. These peaks are responsible for possible unfavourable electrolyte or metabolic effects relating to indapamide blood concentrations. The SR formulation, by eliminating plasma peaks, allows a smoothing of the pharmacokinetic profile of indapamide. This new galenic formulation is based on a hydrophilic matrix tablet composed of a cellulose derivative, methylhydroxypropylcellulose (MHPC), and a binder, polyvinylpyrrolidone (povidone). The originality of the matrix lies in the percentages of MHPC and povidone, which permit a linear release in vitro of indapamide. After optimisation, the chosen ratio of these 2 constituents allowed the release of more than 70% of the dosage over 16 hours in a very reproducible manner. The 2 tested formulations (SR and IR) have the same bioavailability; however, the main pharmacokinetic parameters of the new SR 1.5 mg formulation, calculated after single and repeated administration, show a profile typical of an SR formulation, i.e. a lower maximum concentration (Cmax), a longer time to Cmax, and the same minimum concentration as the IR formulation. This new SR formulation, which allows a reduction in the daily dose of indapamide from 2.5 to 1.5 mg, leads to an improvement in its efficacy/tolerability ratio, thereby meeting the recommendations of the international guidelines for the treatment of essential hypertension.

Biological Availability↗
PubMed2005

Efficacy of combination antihypertensive therapy with low-dose indapamide: assessment by blood pressure self-monitoring at home.

We examined the effects of the addition of low-dose indapamide to antihypertensive drugs of other classes, as well as its duration of action, using blood pressure (BP) self-monitoring at home. Seventy-six patients undergoing monotherapy with a calcium channel blocker (CCB), angiotensin converting-enzyme inhibitor (ACEI), or angiotensin AT1-receptor blocker (ARB), but had an average morning home systolic BP (SBP) > or =135 mmHg or diastolic BP (DBP) > or =85 mmHg, were studied. Indapamide (1 mg) was added to their existing treatment once daily for 4 weeks. The additional hypotensive effects of indapamide were evaluated by casual and home BPs, and the results were compared among the three groups of subjects classified according to their initial drug treatment classes. The morning/evening (M/E) ratio of BP reduction was calculated to assess the duration of the effect. Overall, indapamide significantly (P < 0.001) lowered morning home BP (147 +/- 12/87 +/- 9 mmHg to 135 +/- 12/81 +/- 9 mmHg), evening home BP (138 +/- 15/79 +/- 10 mmHg to 126 +/- 12/73 +/- 9 mmHg), and casual BP (145 +/- 21/86 +/- 14 mmHg to 136 +/- 17/81 +/- 13 mmHg). All groups showed significant indapamide-induced home SBP/DBP decreases, whereas only the ACEI and ARB groups, but not the CCB group, showed a home pulse pressure (PP) reduction. Evening SBP and PP decreases were significantly greater in the ARB group than in the CCB group. The mean M/E ratio with indapamide was 0.95 for SBP and 0.85 for DBP. Low-dose indapamide used in combination can provide additional anti-hypertensive efficacy lasting for 24 h. The added effect of indapamide may be more prominent on ARBs than on CCBs.

Aged↗
PubMed2005

[The comparison of the effect of enalapril and indapamide on the peripheral blood pressure and central blood pressure through pulse wave analysis].

OBJECTIVES: The purpose of this study was to evaluate the effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril and diuretic indapamide on the peripheral blood pressure and the central blood pressure in Chinese patients with essential hypertension. METHODS: This study was a double blind, randomized study. Informed consent were given by all patients. After 2 weeks of placebo run-in period, 105 patients with mild or moderate essential hypertension were randomized to receive either enalapril (10 mg per day) or indapamide (2.5 mg per day) for 8 weeks. Radial pulse wave recordings were performed in all the patients before the active treatments were given and at the end of the study. Only those patients who have finished 8 weeks of active treatment in both groups were included into the final analysis. RESULTS: One hundred one patients (51 in enalapril group and 50 in indapamide group) completed the study. No significant difference (all P values > 0.05) was found in baseline data between the two groups. After 8 weeks of treatment, all the parameters of pulse wave (except heart rates in both groups and augmentation index in indapamide group) decreased significantly. Comparison of the 2 groups showed that there were no significant differences (all P values > 0.05) in all the parameters of pulse wave except that the central systolic blood pressure, augmentation and augmentation index were significantly lower in enalapril group than in indapamide group. In enalapril group, the reduced values of systolic blood pressure and pulse pressure in central aorta were significantly larger than those in brachial artery. However, the difference was not observed in indapamide group. CONCLUSIONS: Enalapril and indapamide are both similarly effective in reducing peripheral arterial blood pressure. Moreover, enalapril is more effective in reducing central systolic pressure and augmentation index than indapamide. The difference is probably due to the reduction of wave reflection caused by enalapril.

Adult↗