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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↗
PubMed1979

Clearance and micropuncture studies of the diuretic xipamide in dogs.

Effects of the diuretic xipamide were examined by clearance and micropuncture techniques, and compared to clorothiazide. Xipamide decreased GFR and phosphate excretion. Reabsorption by superficial proximal tubules was unchanged. Since xipamide reduced single nephron filtration rate and GFR, a small effect on the proximal tubule may have been masked. Chlorothiazide decreased GFR but additionally decreased reabsorption by the proximal tubule. Xipamide was more chloruretic than natiuretic and probably inhibits reabsorption in the distal tubule.

Animals↗
PubMed1980

Clinical trial of xipamide in the treatment of hypertension.

Nine patients with hypertension were given xipamide 40 mg orally as monotherapy on alternate days. An additional seventeen patients had xipamide added to an existing treatment regime of clonidine 450 micrograms per day. Xipamide alone produced a significant fall in blood pressure comparable to that obtained with clonidine alone. However, a significant further reduction was obtained when xipamide was added to the existing clonidine regime.

Administration, Oral↗
PubMed1980

Mathematical model of the time-course of essential hypertension blood pressure changes during chronic xipamide treatment.

The hypotensive effect of xipamide administered at a mean maintenance daily dose of 23.6 mg was studied in 25 essential hypertensive patients during 48 weeks. The mean changes of systolic and diastolic blood pressures in the erect and supine positions from the first week after the onset of treatment onwards were accounted for by monotonically decreasing exponential functions. The hypotensive effect of xipamide achieved clinically satisfactory mean levels within the first week of treatment. The rate of reduction of blood pressure after the first week of treatment with xipamide depended on the inverse of a time-constant, and on the difference between the pre-treatment and the final blood pressure values. In other words, the blood pressure in patients with severe hypertension reached optimal levels more quickly than in patients with moderate and mild hypertension. No statistically significant differences were found between the slopes of the blood pressure changes with time in either body position, and long-term treatment with xipamide did not lead to orthostatic hypotension.

Adult↗
PubMed1981

Comparison of the antihypertensive activities of xipamide and chlorthalidone: a double-blind, randomized, crossover trial.

The effectiveness of a new potent diuretic, xipamide, was evaluated in the treatment of patients with mild to moderate essential hypertension. The effects of daily doses of 40 mg xipamide were compared with those of 100 mg chlorthalidone with respect to systolic and diastolic blood pressure, using a double-blind crossover design. Patients received each drug for 6 weeks, the order of treatments being at random and the periods being separated by a 'washout' period of 7 days. The results showed that xipamide was as effective as chlorthalidone in controlling blood pressure, both in the upright and supine positions, and when administered after chlorthalidone produced a further reduction. No such further reduction occurred when chlorthalidone was given after xipamide. Serum electrolyte changes induced by the two diuretics were comparable. Both drugs were well tolerated and caused few side-effects.

Adult↗
PubMed1982

[Pharmacokinetics of xipamide and triamterene in healthy probands].

Simultaneous detection of 4-chloro-5-sulfamoyl-2',6'-salicyl-oxylidide (Xipamide) and 2,4,7-triamino-6-phenyl-pteridine (Triamterene) in urine specimen of healthy volunteers was achieved by means of a new high performance liquid chromatography (HPLC) method. Pharmacokinetics of both substances in combination (Neotri, dose ratio xipamide: triamterene = 1:3) did not significantly differ from those of the sole substances. Peak urine elimination of unaltered xipamide was 2.5 +/- 0.7 mg/h when given alone and 2.0 +/- 0.7 mg/h in the presence of triamterene. The data for the triamterene excretion were 0.7 +/- 0.1 mg/h and 1.0 +/- 0.3 mg/h, respectively within 1-3 h post application. Assuming a two-compartment pharmacokinetic model the terminal elimination half-lives of unchanged xipamide were 5.3 +/- 1.9 h (monosubstance) and 4.0 +/- 0.6 h (combination). The corresponding data for unchanged triamterene were 6.4 +/- 1.3 h (monosubstance) and 5.5 +/- 1.8 h (combination).

Adult↗
PubMed1975

Xipamid, a potent new diuretic.

The effects of xipamid and frusemide were comapred in 9 oedematous patients. Xipamid was found to be equipotent with frusemide in doses of 40 mg. and 80 mg., with respect to its effect on sodium and water excretion. The time course of action of xipamid was observed to be more prolonged than that of frusemide. It is concluded that xipamid is a potent and safe diuretic.

Adult↗
PubMed1990

Xipamide disposition in liver cirrhosis.

The pharmacokinetics of the sulfonamide-type diuretic xipamide was studied in patients with liver cirrhosis and ascites and compared with healthy control subjects. After oral administration of 40 mg xipamide, the diuretic was rapidly distributed in the blood and the ascites. The ratio of the area under the concentration-time curve (AUC) of plasma and ascitic fluid was 7:2, as was the protein content in the respective compartments. The AUC in plasma of cirrhotic patients was significantly greater than in control subjects (p less than 0.001). The most striking finding was the increase of the amount (Ae) of parent drug and main metabolite excreted into the urine (p less than 0.001). The renal clearance of xipamide was only moderately reduced in patients with liver cirrhosis. Both AUC and Ae were positively correlated to the plasma concentration of direct bilirubin of the patients (p less than 0.05). We concluded that nonrenal drug clearance in patients with liver cirrhosis was reduced as a result of the blockade of hepatobiliary excretion during cholestatic conditions.

Administration, Oral↗
PubMed1981

A study of the antihypertensive action of xipamide using ambulatory intra-arterial monitoring.

1 The antihypertensive activity of the diuretic xipamide has been studied in 18 patients with mild/moderate essential hypertension using the technique of continuous ambulatory intra-arterial blood pressure recording. Full data from 48 h blood pressure recordings before and after treatment were available from 13 patients. 2 After a mean period of 3 months' treatment with xipamide 20 mg once daily, both systolic and diastolic blood pressure were markedly reduced throughout the whole 24 h day, the reductions of systolic being statistically significant throughout the whole period, and of diastolic for 19 out of the 24 hourly periods measured. There was no postural hypotension seen during treatment and there was a conspicuous lack of side effects. 3 Xipamide would appear to be as effective as many beta-adrenoceptor blockers but without their side effects and produces a better control of blood pressure throughout the whole day and night.

Ambulatory Care↗
PubMed2002

Severe electrolyte disturbances and renal failure in elderly patients with combined diuretic therapy including xipamid.

UNLABELLED: Diuretics are among the most frequently prescribed substances in elderly patients, but they are also associated with the highest incidence of adverse effects in this group of patients. Xipamide is a sulfonamide-like diuretic whose action does not depend on transtubular secretion. This characteristic makes it suitable for situations in which the kidney is highly sodium avid. Because of the potency of this substance the risk of adverse reactions like electrolyte disorders or hypovolemia is increased as well. We report seven patients (age 65-85) admitted to the emergency room of the University Hospital of Innsbruck between 1998 and 2002 who had developed serious adverse reactions upon initiation of treatment with xipamide as an additional diuretic. Six of these patients had received combinations with loop diuretics. The disturbances observed were hyponatremia (lowest value 108 mmol/l), hypokalemia (lowest value 1.5 mmol/l) and prerenal azotemia (highest serum urea 269 mg/dl, highest serum creatinine 5.13). CONCLUSION: With the exception of diuretic resistance in severe heart failure or renal insufficiency a combination therapy of xipamide with a second diuretic appears to be associated with an unnecessarily high risk of serious adverse reactions and thus should be avoided. This is especially true for elderly patients.

Age Factors↗
PubMed1988

In vitro effect of xipamide on sodium-potassium transport systems in human erythrocytes.

The in vitro effects of xipamide in a concentration range of 10(-8) to 10(-2) M were investigated on various Na+ and K+ transport systems in human red blood cells. Xipamide inhibited the anion carrier or DIDS-sensitive LiCO3- -influx starting from a concentration of 10(-5) M. However, a decrease in the Na+, K+-pump and the Na+, K+-cotransport activity and a rise in the passive permeability of the cell membrane was only observed starting from a concentration of 10(-4) M xipamide.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1984

A randomized double-blind clinical trial of xipamid and hydrochlorothiazide in essential hypertension.

Seventeen patients with mild to moderate essential hypertension and controlled with antihypertensive drugs were treated with xipamid (40 mg) or hydrochlorothiazide (50 mg) in a double-blind cross-over randomized trial design. After a run-in-period of 2 weeks with placebo, all of them received either of the two drugs. Placebo treatment for 2 weeks decreased both supine as well as standing blood pressure, but it was not statistically significant. Xipamid produced a somewhat greater decrease in blood pressure than hydrochlorothiazide, but the difference was not statistically significant. Similar results were obtained in 12 newly diagnosed cases of mild to moderate essential hypertension treated with xipamid (80 mg) or hydrochlorothiazide (100 mg) daily as single drug treatment in a randomized, double-blind parallel design trial. The side effects produced by both drugs were only mild in nature. No significant changes were produced in serum electrolytes, uric acid and fasting blood glucose in this short term study with either of the drugs.

Blood Pressure↗
PubMed1983

Effect of xipamide and furosemide on guinea pig cochlear recorded potentials.

The effects of furosemide and xipamide on guinea pig cochlear potentials were studied under acute conditions. Auditory nerve action potentials (AP) and cochlear microphonics (CM) were depressed by both diuretics in a dose-related manner. Furosemide was more effective on AP than on CM. In contrast, the xipamide-induced reductions of AP and CM were similar. Our results suggest that the depressive effects of furosemide or xipamide may be related to a direct action on cochlear mechanisms.

Action Potentials↗
PubMed1977

Studies covering combined treatments with xipamide. Results of a long-term antihypertensive treatment.

The antihypertensive active of Xipamide was tested in 23 patients. Xipamide was given in combination with clonidine hydrochloride. The diuretic produced additional reductions in the recumbent blood pressure in 15 patients, and the orthostatic pressure in 19 patients. The antihypertensive action corresponds to those of established diuretics. The same responses were obtained in essential and secondary hypertension. A disadvantage associated with long-term treatment is that of hypokalaemia, which occurs at a dose level of 80 mg Xipamide (double the therapeutic dose). We accordingly recommend a dose of 40 mg, and, as a precaution, regular electrolyte checks. The levels of other side-effects-interference in carbohydrate, lipid, and uric acid metabolism and the rise in blood urea nitrogen are the same as for other diuretics.

Adult↗
PubMed1985

Nadolol in combination with indapamide and xipamide in resistant hypertensives.

Twenty-four hypertensive patients have been studied. All had blood pressure recordings greater than 160/95 mmHg on 3 occasions whilst taking a beta blocker and two other antihypertensive agents in therapeutic doses. Compliance was checked by intermittent urine analysis for the relevant beta-blocker. These difficult to control hypertensives were treated with nadolol alone, nadolol plus indapamide and nadolol plus xipamide each for 2 months in random order. The aim was to reduce the blood pressure to below 160/95 mmHg. The supine blood pressure on nadolol alone (167/100 mmHg) was comparable to that on the previous three drug regimens (157/100 mmHg), the other two treatments were more effective (145/90 and 148/93 mmHg respectively). Hypokalaemia (serum potassium below 3.5 mmol/l) occurred in six individuals but occurred more frequently on xipamide than on indapamide.

Adult↗
PubMed1979

[Rheology of the blood during treatment of hypertension with xipamide (author's transl)].

The possible effect of xipamide on flow properties of blood were studied in groups of eight patients each with essential hypertension. It was demonstrated that 10 mg xipamide (a long-acting diuretic) given daily had no deleterious effect on flow property, while 20 mg daily produced a haemoconcentration which negatively affected it, apparently in relation to the urine volume excreted per unit time. At higher dosages the effect on blood flow properties was shifted in time, which indicates that the increased diuresis in the first day leads to a cumulative effect on the flow properties of the blood. Erythrocyte deformability was not affected. It is possible that combined preparations which contain a diuretic should be specially examined with respect to any undesirable effect on flow properties of the blood.

Aged↗
PubMed1989

A log-dose-response study of xipamide and its effect on metabolic parameters.

An extended dose-response study with xipamide, using seven doublings of the dose, from 0.3125 to 40 mg/day at 4-week intervals, was carried out in 12 hypertensive patients. Blood pressure showed a progressive decline with doses from 5 to 20 mg, and 40 mg xipamide produced no greater fall. Some subjects showed a maximum fall in blood pressure with a single dose increase but most showed a declining blood pressure over two or more dose increases. Plasma urea increased with doses of 5-40 mg to a similar extent, but there was no fall in the mean potassium level except with the 40-mg dose. Urinary calcium was reduced (from 4.2 to 1.7 mmol/24 h) on the 40-mg dose and the corrected plasma calcium level rose from 2.28 to 2.32 mmol/l. Triglycerides, very-low-density lipoprotein cholesterol and plasma aldosterone increased at the maximum dose; the cholesterol ratio, however, was unchanged.

Blood Pressure↗