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At least 19 recordsLinked to original sources
PubMed1990

[Photosensitivity following enoxacin and xipamide: combined phototoxic and photo-allergic reaction to enoxacin, photo-allergic reaction to xipamide with subsequent transient light reaction].

In a 51-year-old female patient, we observed a combined phototoxic and photoallergic reaction to Enoxacin, a photoallergic reaction to Xipamide, as well as increased sensitivity to light after withdrawal of the drugs. This unusual diagnosis was based on the clinical picture, graded radiation with UV-A and UV-B, the irradiated intradermal assay, and histological findings. To the best of our knowledge, this is the first report on a photoallergic reaction to Xipamide associated with a combined phototoxic and photoallergic reaction to Enoxacin.

Biopsy↗
PubMed1989

Plasma atrial natriuretic peptide and the renin-aldosterone system during long-term administration of the diuretic xipamide in man.

We have studied the effect of xipamide on plasma alpha-atrial natriuretic peptide and the renin-aldosterone-kallikrein system in twelve healthy men, using a double-blind cross-over design. After a run-in period on placebo for 1 week the subjects were treated with either placebo (n = 6) or xipamide 20 mg once daily (n = 6) for 16 weeks and were then switched to the alternative medication for another 16 weeks. The plasma concentration of alpha-atrial natriuretic peptide fell after 1 week of xipamide administration and increased during prolonged xipamide administration but remained suppressed. The changes in plasma alpha-ANP observed after 1 week of xipamide were negatively correlated with the changes in haematocrit and haemoglobin. Plasma renin activity (PRA), aldosterone concentration (PAC), and urinary excretion of aldosterone and kallikrein increased after 1 week of xipamide administration, levelled off during the second and fourth weeks, but remained elevated during further prolonged xipamide administration for 16 weeks. The xipamide-induced changes in PRA and PAC were positively correlated with the changes in the haematocrit and haemoglobin. Our data suggest that the changes in plasma renin, aldosterone, and alpha-atrial natriuretic peptide during xipamide administration may be related to diuretic-induced volume contraction.

Aldosterone↗
PubMed1991

Hormonal effects of the diuretic xipamide in healthy men.

The effect of xipamide on plasma alpha-atrial natriuretic peptide and the renin-aldosterone-kallikrein system have been studied in 12 healthy men, using a double-blind cross-over design. After a run-in period on placebo of 1 week, the subjects were treated with either placebo (n = 6) or xipamide 20 mg once daily (n = 6) for 16 weeks and were then switched to the alternative medication for another 16 weeks. The plasma concentration of alpha-atrial natriuretic peptide fell after 1 week of xipamide administration and increased during prolonged xipamide administration but remained reduced. The changes in plasma alpha-ANP observed after 1 week of xipamide were negatively correlated with the changes in hematocrit and hemoglobin. Plasma renin activity (PRA), aldosterone concentration (PAC), and urinary excretion of aldosterone and kallikrein increased after 1 week of xipamide administration, levelled off during the second and fourth weeks, but remained elevated during further prolonged xipamide administration for 16 weeks. The xipamide-induced changes in PRA and PAC were positively correlated with the changes in the hematocrit and hemoglobin. The changes in plasma renin, aldosterone, and alpha-atrial natriuretic peptide during xipamide administration may be related to diuretic-induced volume contraction.

Adult↗
PubMed1982

Xipamide and cyclopenthiazide in essential hypertension--comparative effects on blood pressure and plasma potassium.

1 The blood pressure lowering effect of xipamide, a non-thiazide diuretic given for 6 weeks was compared in a randomised cross-over trial with that of cyclopenthiazide in 14 patients with essential hypertension. 2 Xipamide 10 or 20 mg given once daily was as effective in lowering supine blood pressure as daily cyclopenthiazide 0.5 mg. There was no difference in the blood pressure lowering effect of 10 mg xipamide daily for 2 weeks compared to 20 mg daily given for a further 4 weeks. 3 Plasma potassium was reduced by both drugs, but markedly more after both 10 mg and 20 mg xipamide than after cyclopenthiazide 0.5 mg. By the sixth week of treatment 13 of 14 patients on xipamide but only 6 of 14 on cyclopenthiazide has plasma potassium concentrations of, or less than, 3.5 mmol/l. The fall in plasma potassium was significantly greater and the final plasma potassium concentration was significantly lower after either dose of xipamide than after cyclopenthiazide. 4 These results suggest that 10 mg or 20 mg of xipamide daily is effective in lowering blood pressure in hypertensive patients but is associated with hypokalaemia. In view of recent evidence linking diuretic-induced hypokalaemia with cardiac dysrhythmias in patients with essential hypertension we would suggest that thiazide diuretics be used in preference to xipamide for the routine management of essential hypertension. Our results also suggest that the currently recommended dose of xipamide (20 mg) for the treatment of hypertension is excessive, and lower amounts than 10 mg per day might possibly be as effective in lowering blood pressure with less adverse metabolic consequences.

Adult↗
PubMed1990

[Beneficial effects of xipamide on pH and Ca2+ ions of cardiac cells].

We have shown that xipamide is the only antihypertensive agent able to selectively inhibit the anion exchanger (AE), a transport system translocating (i) chloride and bicarbonate (thus participating to internal pH), but also (ii) Na+ as NaCO3-(which could explain the natriuretic effect of xipamide). On the other hand, Ollivier (Val de Grâce, Paris) has shown that xipamide exerts a beneficial action on heart by favoring left ventricular relaxation in essential hypertensive patients exhibiting cardiac hypertrophy. In order to understand this clinical effect, we have studied the effect of xipamide on pH and cytosolic free calcium in cultured Rat cardiocytes (H9c2 line). pHi was measured at equilibrium using 14C-DMO and cytosolic free calcium was measured spectrofluorimetrically with Fura2 (Shimadzu RF 5000). 1) The presence of bicarbonate induced a 0.39 +/- 0.14 (mean +/- SD; n = 3) alkalinization; final pHi was 7.08 +/- 0.15 (n = 8). Nor 20 microM DIDS (specific AE inhibitor), neither 50 microM xipamide were able to modify this result. This suggests that the alkalinization is not due to the anion exchanger. 2) After preincubation in the presence of 0.5 microM DIDS, we observed a 0.35 +/- 0.21 acidification (n = 4). Conversely, 0.5 microM xipamide induced a 0.22 +/- 0.16 alkalinization (n = 4). 3) Xipamide (0.5-500 microM) increased the internal K/Na ratio (at 0.5 microM, delta = 3.1 +/- 0.2; n = 3); this was mainly due to internal K+ increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Xipamide. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy.

Xipamide is a diuretic derived from salicylic acid and has a structural resemblance to chlorthalidone. Its pharmacodynamic profile shows a diuretic efficacy is similar to that of frusemide (furosemide) at doses up to 40 mg, but the onset and duration of action are comparable to those of hydrochlorothiazide. Xipamide has been studied mostly in the treatment of mild to moderate essential hypertension, with few controlled studies of its use in oedematous states. The efficacy of xipamide 20 to 40 mg once daily in patients with mild to moderate hypertension is comparable to that of bendrofluazide 5 mg, bumetanide 1 mg or hydrochlorothiazide 50 mg when used alone in newly treated or previously treated patients. The addition of xipamide 20 to 40 mg daily to regimens containing beta-blockers, adrenergic neuron-blocking drugs and/or methyldopa has resulted in a further reduction in blood pressure. A few studies in oedematous states suggest that xipamide 40 to 80 mg is comparable in efficacy to equal doses of frusemide, and that the side effects of hypokalaemia, hyperuricaemia and increased blood glucose in diabetics or latent diabetics are similar to those of other diuretics. Thus, xipamide is a suitable alternative to other diuretics in the treatment of mild to moderate hypertension and combines the efficacy of frusemide with a less abrupt action in the treatment of oedema.

Animals↗
PubMed1984

The magnesiuric effects of several single doses of xipamide in healthy adults.

Common diuretics induce hypermagnesiuria which may lead to somatic magnesium depletion and subsequently to serious cardiac arrhythmias. The objectives of the present study were to determine if low doses of the diuretic xipamide cause hypermagnesiuria and to describe the time course of urinary Mg2+ excretion after xipamide in normal probands. Experiments were carried out on 13 healthy adult volunteers given monodoses of placebo, 5, 10 and 20 mg xipamide on separate days in random order. Urine collected at 3, 6, 12 and 24 h after dosing was analyzed for Mg2+ and other solutes. All doses of xipamide induced significant increases of 24-h urinary volume, and C1-, Na+, K+ and Mg2+ excretion when compared to the placebo. Urinary Mg2+ flow was delayed with respect to Na+ flow for all doses of xipamide. Xipamide administered acutely at low doses to healthy subjects causes hypermagnesiuria. The likelihood exists that this substance may induce somatic magnesium depletion when chronically administered, even at low doses.

Adult↗
PubMed1981

Hypotensive effects of xipamide in essential hypertension. Crossover comparison with hydrochlorothiazide.

Twenty-nine patients with mild to severe essential hypertension were treated with titrated doses of xipamide, before or after treatment with 50 and , if necessary, 100 mg hydrochlorothiazide in a 13- to 25-week open crossover study. Based on supine diastolic pressure readings taken at weekly intervals, xipamide controlled hypertension in all subjects: 17 achieved control with a daily dose of 5 mg; seven, with 10 mg; and five, with 20 mg. In contrast, eight of the 29 patients could not be controlled with 100 mg/day hydrochlorothiazide. The only significant biochemical change observed was an increase in serum uric acid in 12 patients after hydrochlorothiazide but in only six patients after xipamide. Natriuresis was comparable after both drugs; 5 and 10 mg xipamide were as effective as 50 and 100 mg hydrochlorothiazide. The only side effect noted, cramping due to hypokalemia, occurred during treatment with hydrochlorothiazide, but not xipamide, and was reversed by potassium supplements.

Adult↗
PubMed1984

Pharmacodynamics and pharmacokinetics of xipamide in patients with normal and impaired kidney function.

The effect of a single oral dose of 40 mg xipamide on urinary excretion of Na+, K+, Cl-, Ca2+ and Mg2+ in healthy subjects and in patients with varying degrees of renal impairment was compared with various conventional diuretics. Xipamide caused marked excretion of Na+ and Cl-, whereas the diuretic produced only moderate kaliuresis; urinary excretion of Ca2+ was increased in proportion to Na+, like the loop diuretics. Xipamide affected electrolyte excretion even in patients with a creatinine clearance below 30 ml/min, as do the loop diuretics, too. Therefore, the pharmacodynamic characteristics of xipamide are more like those of a loop diuretic than of a thiazide. Xipamide was good bioavailable, its t 1/2 beta was 7 h and urinary recovery of the undegraded drug was 40% of the given dose. In renal insufficiency, t 1/2 beta increased from 7 to only 9h, yielding a moderate increase in the AUC. Urinary recovery of the drug was reduced in proportion to the reduction in the creatinine clearance of the patient. Therefore, significant extrarenal elimination of the diuretic must be postulated, which suffices to prevent significant drug accumulation in renal failure.

Adult↗
PubMed1987

Inhibition of the Cl-/NaCO3- anion exchanger by xipamide in human red blood cells.

The mechanism of action of classical loop diuretics of the 2- or 3-amino-5-sulfamoylbenzoic acid and (aryloxy)acetic acid families involves competition with chloride for a common site on the (Na+, K+, 2Cl-) co-transport system. However this is not the mechanism of action of some high-ceiling diuretics like muzolimine, MK 473, xipamide, indapamide and clopamide, which are not carboxylic acids. We evaluated three of these latter diuretics (xipamide, muzolimine and clopamide) for their inhibitory effects on five ion transport systems in human red blood cells: (i) Cl(-)-dependent (Na+, K+) co-transport, (ii) (NaCO3-/Cl-) anion exchanger, (iii) (Cl-, K+) co-transport, (iv) Na+, K+ pump and (v) Na+: Li+ counter-transport; and on one ion channel the Ca2+-dependent, K+ channel. All erythrocyte transport pathways were resistant to the three diuretics studied (IC50 of 10(-3) M or higher) with one remarkable exception, the (NaCO3-/Cl-) anion exchanger. This transport system was inhibited by xipamide (IC50 of 2.5 +/- 0.4 X 10(-5) M, mean +/- S.D. of five experiments) and less potently by muzolimine (IC50 of 1.1 +/- 0.3 X 10(-4) M, mean +/- S.D. of three experiments). Clopamide only inhibited the anion exchanger at high concentrations (IC50 of about 10(-3) M). Xipamide, the most potent diuretic in this test, was at least one order of magnitude more active than furosemide, ethacrynic acid, hydrochlorothiazide and amiloride. Inhibition of the anion carrier could be involved in the diuretic action (inhibition of CO2-stimulated NaCl absorption in the TAL) and/or in the antihypertensive action (inhibition of net NaCO3- influx and secondarily of Ca2+ influx through Na+: Ca2+ exchange in vascular smooth muscle cells of xipamide).

Bicarbonates↗
PubMed1982

Effect of xipamide in oedema of renal disease with varying degrees of renal insufficiency: a comparative trial with frusemide.

In an open crossover trial, 15 patients with evidence of renal impairment, defined by proteinuria, raised serum creatinine or impaired creatinine clearance, were randomly allocated to treatment with either 40 mg frusemide or 40 mg xipamide daily for 7 days. After a 3-day mid-point wash-out period, patients were changed the alternative drug for a further 7 days. Assessment measures involved a wide range of clinical and biochemical parameters. Whilst both drugs significantly reduced oedema, xipamide was more effective than frusemide, and this was associated with a significantly greater effect on sodium excretion with xipamide. With the exception of standing systolic blood pressure where the reduction was significantly more pronounced with xipamide, no significant changes in resting systolic, resting diastolic or standing diastolic pressure were observed to be associated with change of treatment. Three patients noticed minor side-effects during xipamide therapy. There were no adverse reactions inpatients taking frusemide.

Adolescent↗
PubMed1977

[Studies on Xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide). Part 1: Physico-chemical and chemical properties (author's transl)].

The saluretic agent xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide; Aquaphor) is a lipophilic substance as demonstrated by solubilities and partition coefficients. In the physiological pH-range, however, xipamide forms an anion which has an octanol-water partition coefficient of approx. 1. Two steps of ionization were investigated photometrically. The first one gives rise to a phenolate anion; pKa1 = 4.75. In the second one, ionization of the sulfamoyl group occurs; pKa2 = 10. Xipamide is stable in acidic as well as in basic media at room temperature. But when xipamide is acted upon by strong alkali and elevated temperature, 2,6-xylidine is formed by hydrolysis. For analytic use UV-photometric, colorimetric and TLC data of xipamide are given.

Chemical Phenomena↗
PubMed1989

Erythrocyte sodium and potassium transport systems during longterm administration of the diuretic xipamide in men.

The effects of xipamide on the intracellular concentration and transmembrane fluxes of Na+ and K+ were studied in twenty-four normal sodium-replete or -deplete male subjects, using a double-blind study design. After a run-in period on placebo for 1 week on their regular diet, subjects were treated on their regular diet or on a low-sodium diet with either placebo or xipamide 20 mg once a day for 16 weeks. Intra-erythrocyte Na+ concentration was increased during xipamide administration in sodium-replete and deplete subjects, while intra-erythrocyte K+ and total intraleukocyte Ca2+ concentrations were decreased. Red cell Na+, K+-cotransport activity was lower in xipamide-treated subjects, while Na+, Li-countertransport activity was increased. No significant effect of xipamide could be demonstrated on ouabain-sensitive 86Rb-uptake or on maximal [3H]-ouabain binding in erythrocytes.

Adult↗
PubMed1983

Once daily administration of low-dose xipamide: a long-term study in mild to moderate hypertension.

The anti-hypertensive effects of xipamide in doses of 5-20 mg once daily were studied in a multicenter study. Three general practitioners recruited 74 patients with uncomplicated hypertension. After a run-in period, patients entered a dose-ranging study and were followed for an average period of 10.4 months. Supine and standing blood pressures were significantly decreased (22.2/14 and 21/14 mmHg) during xipamide therapy with average daily dose of 12.2 mg. Serum potassium values dropped from 4.43 +/- 0.06 to 3.96 +/- 0.5 mEq/l, and serum uric acid increased from 5.47 +/- 0.06 to 6.04 +/- 0.18 mg%. In a second part 47 patients entered a double-blind, crossover study of placebo. Their optimum xipamide doses confirmed that in the majority of patients with mild to moderate hypertension xipamide in doses lower than 20 mg is effective in lowering blood pressure. The study further confirmed that xipamide exerted its anti-hypertensive effects for at least 24 h.

Adult↗
PubMed1983

[Saluretic and diuretic effects of xipamide-triamterene combinations in varying dose ratios in rats].

The saluretic and diuretic properties of 4-chloro-5-sulfamoyl-2',6'-salicyloxylidide (xipamide) and 2,4,7-triamino-6-phenyl-pteridine (triamterene) were determined in rats following sole and combined application in various dosages and dose ratios. Xipamide dosages ranged from 0.01-30 mg/kg body weight. Xipamide, when given alone, revealed a significant dose-dependent increase in sodium excretion and urine volume compared to control animals even in the smallest dose to be tested (0.01 mg/kg). Triamterene as sole agent led to an increased sodium and water excretion when given in a natriuretic threshold dose of approximately 1.0 mg/kg. Potassium excretion was slightly enhanced following xipamide application and decreased significantly with triamterene treatment. The combined application of xipamide and triamterene in dose ratios of 1:1-1:4 (xipamide/triamterene) resulted in an increased sodium excretion which was almost additive following high triamterene dosages. Potassium elimination decreased significantly when threshold triamterene dosages were added. High triamterene dosages in all dose ratios of the combined application resulted in potassium levels which only could be registered following sole triamterene application.

Animals↗
PubMed1980

[Dose-response relationship of xipamide in healthy subjects].

To establish a dose-effect relationship for the xipamide diuretic in double-blind trials 0, 5, 10, 20 and 40 mg of xipamide were administered to 5 groups of 6 to 14 healthy test persons in each group. Before, during and after the 15-d period of application all the blood electrolytes as well as the metabolism parameters of glucose, uric acid, cholesterol, neutral fats as well as creatinine and urea were determined. Similarly during the entire period of investigation the 24-h urine samples were collected daily and from these the electrolyte excretion as well as the endogenic creatinine clearance were determined. It was found that diuresis and natriuresis significantly enhanced in comparison with placebo were already achieved with 5 mg xipamide per day, they could no further be increased by higher doses. Much rather at 40 mg xipamide per day a significant hypokalaemia as well as a light hypercalcaemia developed. Independently of the dose, during the period of investigation a light, fully compensated hypochloraemic alkalosis developed. Regarding the metabolic processes a slight increase in the uric acid and cholesterol blood levels was observed, while the blood-sugar level, the triglycerides as well as the endogenic creatinine clearance remained unaffected. It can be concluded from the investigations that maximum natriuresis and diuresis can already be achieved with a daily xipamide dose of 5 mg, while side effects can be kept at a minimum.

Adult↗
PubMed1975

[Pharmacological and toxicological properties of the saluretic xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide)].

Xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide, Aquaphor), a new compound is a derivate of salicylic acid with marked sodium and water excreting potency. Its effect is dosage dependent. Dosages as low as 0.001 mg/kg p.o. in rats and 0.04 mg/kg p.o. in dogs lead to a statistically significant increase of sodium and water excretion. Potassium excretion was less affected and showed to be rather constant in a dosage range between 0.01 and 10.0 mg/kg. In rats a maximum of sodium and water excretion could be reached by a dose of 200 mg/kg duration of action in rats was approximately 10 h. In dogs a statistically significant sodium and chloride excretion could be detected after oral application of 0.04 mg/kg. Xipamide increased diuresis started with an oral dose of 0.1 mg/kg. Intravenous application of xipamide in a dose of 0.2 mg/kg in dogs accompanied by permanent infusion of 5 per cent mannit solution clearly showed the diuretic profile of the substance: increased diuresis started within 40 min. A peak was reached within 40-60 min post injectionem. Then excretion decreased slowly. Even 120 min post injectionem a diuretic action could be detected. Diuresis and sodium excretion could be demonstrated in rats with experimentally predamaged kidneys and with steroid dependent sodium retention. As could be demonstrated in hypertensive rats xipamide had a hypotensive effect, normotensive rats were not affected. In animal studies xipamide was excellently tolerated. The therapeutic range of the substance was high in single doses as well as when the drug administered over 6 weeks.

Animals↗
PubMed1979

Site of renal action of xipamide.

Xipamide, hydrochlorothiazide, and furosemide were given to normal volunteers on a double-blind basis. During maximal water diuresis, there was a reduction in free water clearance and an increase in osmolar clearance after administration of xipamide and hydrochlorothiazide, but not in the case of furosemide. During maximal hydropenia, both xipamide and hydrochlorothiazide increased free water reabosorption in a linear relationship to osmolar clearance, while furosemide increased osmolar clearance with little change in free water reabsorption. It was concluded, therefore, that, as with hydrochlorothiazide, the site of action of xipamide was on the distal convoluted tubule, and that of furosemide on the loop of Henle.

Diuresis↗