Assessment of the genotoxic effects of antihypertensive drug active ingredient indapamide in human lymphocytes.

Hypertension is the most common cardiovascular disease and is also known as high blood pressure. The large majority of hypertensive patients need long-term administration of antihypertensive agents. Indapamide is an orally administered diuretic antihypertensive drug. The present work aimed to assess the possible genotoxic effects of indapamide using four different assays: chromosomal aberration (CA), sister chromatid exchange (SCE), micronucleus (MN), and comet. Lymphocytes from three different donors were exposed to 18.75, 37.50, 75.00, and 100.00 µg/ml indapamide. Additionally, a negative, a positive (mitomycin C = MMC, 0.20 µg/ml), and a solvent control (5.4 µl/ml methanol) were also applied. As a result, it was seen that indapamide did not cause a significant change in CAs and MN frequencies compared to the control. It caused significant damage only at the highest concentration in the comet assay. Similarly, while it did not affect the number of SCEs in the 24-h treatment, it increased the SCE frequency at the two highest concentrations in the 48-h. Mitotic index (MI) decreased at almost all concentrations. Considering all these results, this study revealed that indapamide did not have a significant genotoxic effect in these conditions. To the best of our knowledge, this is the first investigation about the genotoxic effect of indapamide in human lymphocytes in vitro.

Gender-related differences in drug-induced prolongation of cardiac repolarization in prepubertal guinea pigs.

Underlying mechanisms of drug-induced long QT syndrome are not fully understood. Our objective was to evaluate gender-related differences for block of the rapid (I(Kr) ) or/and the slow (I(Ks)) components of the delayed rectifier potassium current in prepubertal male and female guinea pigs (n = 120) treated with or without verapamil. Indapamide (I(Ks) blocker) prolonged the monophasic action potential duration at 90% repolarisation (MAPD( 90)) in females more than in males (15.1 + 0.5 vs 9.7 + 1.3 msec; P < .05) in verapamil treated animals. In contrast, MAPD(90) prolongation induced by domperidone or dofetilide (I(Kr) blockers) was not different between genders. Verapamil treatment augmented prolongation of MAPD( 90) caused by dofetilide or domperidone (P < .01). In conclusion, 1) females exhibited greater prolongation of MAPD(90) when exposed to indapamide, 2) no gender-related differences were observed for I( Kr) blockers, and 3) verapamil treatment did not uncover gender-related differences in I(Kr) or I(Ks) block, although it augmented prolongation of cardiac repolarization by I(Kr) blockers.

[Hypotensive effectiveness and metabolic effects of indapamide in patients with primary arterial hypertension]. / Skutecznosc hipotensyjna i wplywy metaboliczne indapamidu u chorych na nadcisnienie tetnicze pierwotne.

Indapamide--a non-thiazide diuretic agent--was given to 28 patients with mild and moderate hypertension in a daily dose of 2.5 mg for 12 weeks. Statistically significant decrease in both systolic and diastolic blood pressure and complete normalization of the arterial blood pressure were achieved in 82% of the treated patients. Adverse reactions were mild and transient. However, low but statistically significant decrease in blood serum potassium and changes in the carbohydrate metabolism were seen. No significant effect of the-drug on lipid metabolism was found except the low but statistically significant increase in total cholesterol. Indapamide is an efficient and well tolerated hypotensive agent. However, biochemical indices should be checked up during the treatment due to the potential adverse reactions.

Indapamide. A review of its pharmacodynamic properties and therapeutic efficacy in hypertension.

Indapamide is an orally active sulphonamide diuretic agent. Although some evidence appears to indicate that the antihypertensive action of indapamide is primarily a result of its diuretic activity, only a limited diuresis occurs with the usual antihypertensive doses of 2.5 mg daily, and in vitro and in vivo data suggest that it may also reduce blood pressure by decreasing vascular reactivity and peripheral vascular resistance. In mild to moderate hypertension it is as effective as thiazide diuretics and beta-adrenergic blocking agents in lowering blood pressure when used as the sole treatment. Indapamide has been successfully combined with beta-adrenergic blocking agents, methyldopa, and other anti-hypertensive agents. While such findings need confirmation, it appears that indapamide shares the potential with other diuretic agents to induce electrolyte and other metabolic abnormalities, although it may do so with less frequency or severity. Thus, indapamide appears to offer a suitable alternative to more established drugs as a 'first-line' treatment in patients with mild to moderate hypertension. Whether it differs significantly from other diuretics when used as antihypertensive therapy, either in its mode of action or its side effect profile, needs further clarification.

Antihypertensive action of indapamide. Comparative studies in several experimental models.

1-(4-Chloro-3-sulfamylbenzamido)-2-methyl-indoline (indapamide), after single oral dose administration, showed antihypertensive activity in genetically hypertensive rats, DOCA/saline hypertensive rats, unilaterally-nephrectomised DOCA/saline hypertensive rats and dogs made hypertensive by renal encapsulation. The activity was observed at doses as low as 1-3 mg/kg and lasted at least 48 h. Increasing the dose level considerably prolonged the duration of action but did not substantially enhance the maximum antihypertensive effect. In genetically hypertensive rats indapamide was 30-300 times more potent than furosemide, spironolactone and chlorthalidone. Indapamide had no effect on blood pressure in normotensive rats. In concentrations of 1 X 10(-5) to 1 X 10(-3) g/ml, indapamide antagonised contractions of arterial and venous strips to angiotensin, epinephrine and norepinephrine revealing a direct vascular action. Indapamide has a prolonged saluretic action which in combination with the direct vascular effects may well account for its antihypertensive activity.