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At least 19 recordsLinked to original sources
PubMed1982

New design for clinical trial of antihypertensive drugs applied to pindolol, clopamide, and combinations thereof.

A beta-blocker (pindolol) and a diuretic (clopamide) were given in different dosages, singly and in two different combinations, to 71 patients with mild to moderate essential hypertension. The trial design was such that patients took both drugs singly and in combination, and in different doses, according to a set plan. The best regimen for each patient was determined by taking into account not only blood pressure but also resting heart-rate, body-weight, serum potassium, and serum urate. For 19 patients (27%) monotherapy was best--pindolol for 16 and clopamide for 3. For the remaining patients, a combination of pindolol 10 mg and clopamide 5 mg was best for 39, and in 35 of these one tablet daily was sufficient. All patients reached the preset target blood-pressure. The differences in proportions responding best to the following pairs of regimens compared--monotherapy vs combination, and combination of clopamide 5 mg and pindolol 5 mg vs combination of clopamide 5 mg and pindolol 10 mg--were significant (2p less than 0.01). The process by which the best treatment is chosen according to this study design resembles much more closely that followed in general medical practice, than does the process in the conventional hypertension trial, in which only average effects are reported and compared.

Adult↗
PubMed1984

A dose-finding study of the combination of pindolol, clopamide and endralazine in the treatment of moderate-to-severe hypertension.

This study compared the efficacy of a beta-blocker, pindolol, and a diuretic, clopamide, plus a vasodilator, endralazine, in the treatment of 30 patients suffering from moderate-to-severe hypertension. Different doses of endralazine were tested. This study showed that hypertension was controlled in 76,7% of patients receiving a combination of pindolol 10 mg and clopamide 5 mg (Viskaldix; Sandoz) plus endralazine 5 mg, and in 90% it was controlled by a combination of pindolol 10 mg, clopamide 5 mg and endralazine 10 mg daily. In 3 patients it was necessary to give pindolol 10 mg, clopamide 5 mg and endralazine 10 mg twice daily. Side-effects occurred in 5 patients, but they were not sufficiently severe for discontinuation of the therapy. There was no difference as regards the blood pressure response in the 15 Black and 15 Indian patients. Tolerance over a period of 14 weeks did not occur. Results of this study suggest that a fixed drug combination of pindolol 10 mg, clopamide 5 mg and endralazine 10 mg once daily could control blood pressure in about 90% of patients suffering from moderate-to-severe hypertension.

Antihypertensive Agents↗
PubMed1987

Clopamide: plasma concentrations and diuretic effect in humans.

Clopamide pharmacokinetics were determined after oral doses of 5, 10, and 20 mg in normal volunteers. Maximum plasma concentrations occurred within 2 hours and were followed by a monoexponential decline with an elimination half-life of approximately 10 hours. There was an approximately linear relationship between dose and the AUC. Urinary sodium, chloride, and potassium excretion rates indicated that the peak diuretic activity corresponded with peak plasma drug concentrations and probably continued for 12 to 24 hours. There was little difference between the total sodium and chloride output after each dose of clopamide, suggesting that 5 mg may have been close to the top of the dose-response curve. Chlorothiazide, 500 mg, caused less sodium and chloride output with similar potassium loss. During chronic administration to patients with hypertension, hypokalemia was more marked with clopamide, 10 mg daily, than with clopamide, 5 mg, or chlorothiazide, 500 mg daily.

Administration, Oral↗
PubMed1987

Effects of pindolol and clopamide on blood lipids in arterial hypertensive patients.

The effects of clopamide, pindolol and its combination on plasma lipids in 49 hypertensive patients (WHO I-II), divided into three parallel randomized groups, were studied over a 6 months period. Total cholesterol, triglycerides, HDL and LDL cholesterol fractions were determined twice during an initial 4-week washout phase, and after a 1-, 3- and 6-month active hypotensive drug phase. Patients were instructed to maintain their usual dietary habits. Daily drug doses were adjusted progressively to attain optimal hypotensive effects. In the clopamide monotherapy group, total cholesterol increased significantly (p less than 0.05); triglycerides and LDL showed a tendency to increase while for HDL a tendency to decrease was observed. In the pindolol monotherapy group, a significant reduction of triglycerides (p less than 0.01) and a significant increase of HDL cholesterol (p less than 0.05) were recorded. No significant changes in total cholesterol or LDL fraction were observed. Combined pindolol-clopamide therapy decreased total triglycerides (NS), increased HDL significantly (p less than 0.05) and did not influence total cholesterol and LDL fraction. It is concluded that pindolol does not negatively influence blood lipids as the thiazide-type diuretic clopamide does, and that when both drugs are used together, the beta-blocker can probably counterbalance the diuretic-induced negative effects on blood lipids. Accordingly, it is suggested that pindolol could be a more favorable beta-blocker drug to be used on hypertensive subjects with metabolic coronary risk factors.

Adult↗
PubMed1991

Effect of clopamide, a thiazide diuretic, on copper and zinc levels in hypertensive patients.

Thiazide diuretics, which are often prescribed to treat mild to moderate hypertension, commonly cause an increase in urinary zinc (Zn) excretion. Metabolic interrelationships between Zn and copper (Cu) are known to exist; consequently, Zn might influence Cu levels. This study aims to determine whether or not Cu and Zn levels in hypertensive patients were influenced by treatment with clopamide, a thiazide diuretic. Eight male patients, aged 36-59 and with an average supine diastolic pressure of 95-115 mm Hg, were treated with single daily doses of clopamide 5 mg as monotherapy for 16 weeks. Plasma, erythrocyte (RBC), and mononuclear leukocyte (WBC) levels of Cu and Zn were determined immediately before therapy (week 0) and again at weeks 8 and 16. There was a significant fall in Cu in mononuclear WBCs from 13.25 (SEM = 0.86) to 1.9 fg/cell (SEM = 0.56) (p less than 0.001) and an increase in Zn from 33.87 (SEM = 3.7) to 70.8 fg/cell (SEM = 11.7) (p less than 0.001), with no change in either cell count or measurable cell volume. Plasma Cu levels increased significantly (p less than 0.001), but the Zn levels decreased only slightly (p less than 0.03). Changes in RBC Cu levels during the treatment period were not significantly altered (p less than 0.1). Zn levels in RBCs were significantly (p less than 0.04) lower. It is concluded that treatment with clopamide may induce some changes in Cu and Zn levels in normal hypertensives, particularly in WBCs. Further investigation is needed to determine the extent of this influence.

Adult↗
PubMed1979

Two-years' study with a combination of pindolol and clopamide ('Viskaldix') in patients with moderate hypertension.

A study was carried out to evaluate the long-term effects and side-effects of a combination product containing the beta-blocker pindolol (10 mg) and the diuretic clopamide (5 mg) in 15 patients with moderate hypertension. All patients completed the 2-years' study. The dose of the combination was increased until blood pressure normalized or a maximum dose of 3 tablets (equivalent to 30 mg pindolol and 15 mg clopamide) daily was reached. Blood pressure and heart rate were recorded monthly and detailed medical examinations were done regularly throughout the study. A mean dose of 2 tablets of the combination product (20 mg pindolol and 10 mg clopamide) produced a significant reduction in blood pressure. In all but 1 patient, blood pressure control was achieved and maintained. No tolerance developed. Heart volume showed a marked decrease. No side-effects of clinical importance were noted.

Adult↗
PubMed1978

[A field study with the combination of Pindolol and Clopamid in antihpertensive therapy (author's transl)].

In a field study comprising 678 patients with arterial hypertension efficacy and tolerance of the stable combination VKB 105 consisting of 10 mg Pindolol (Visken) and 5 mg Clopamid (Brinaldix) were investigated. Treatment with 1--2 tablets of VKB per day resulted in a successful therapy in 94% of all patients corresponding on the average to a reduction in blood pressure to 145/85 mm Hg within 14 days. In mean arterial pressures ranging between 120 and 170 mm Hg a positive linear relationship between the individual initial value and the hypotensive effect of the combination could be observed. A controlled omission trial disclosed qualitatively the respective contribution to the effect of the two components Pindolol and Clopamid. With a systematic case control of the serum potassium under the combined therapy with VKB 105 and during a monotherapy with Clopamid and antihypokalaemic effect of Pindolol could be demonstrated diminishing the tendency for potassium loss. The result revealed a far-reaching potassium neutrality of diuresis-depending stimulation of renin by the beta-receptor blocker. In 61 patients altogether subjective side-effects could be recorded, such as vertigo (5%), palpitations (2.8%), fatigue (2%), insomina (1.9%), nausea (1.7%) and vomiting (0.8%). Laboratory controls gave no indication for clinically relevant changes.

Adrenergic beta-Antagonists↗
PubMed1982

Renal tubular secretion and effects of chlorothiazide, hydrochlorothiazide and clopamide: a study in the avian kidney.

The relationship between renal tubular secretion and saluretic effects of two thiazides (chlorothiazide and hydrochlorothiazide) and clopamide was studied using a modified Sperber technique. The distribution of carbonic anhydrase in the avian kidney was studied by a histochemical method. The modified Sperber technique allows an absolute estimation of the tubular excretion efficiency of a substance, as determined by its True Tubular Excretion Fraction (TTEF). The TTEF values were for chlorothiazide 59%, hydrochlorothiazide 22% and clopamide 10%. Thus, they were all actively secreted by renal tubular cells; most likely through organic anion transport since novobiocin markedly reduced the TTEF values. After infusion of the diuretics into the renal portal system on one side there was only a small ipsilateral excess natriuresis and chloruresis, in spite of their different tubular excretion efficiencies. For hydrochlorothiazide, and especially for chlorothiazide the saluretic effect therefore appears to be largely independent of the tubular fluid concentration of the diuretic and primarily evoked from the peritubular side of the avian nephron. This is a sharp contrast to the primarily luminally induced saluretic effects of furosemide, ethacrynic acid and piretanide. Only chlorothiazide caused an ipsilateral excess excretion of potassium and bicarbonate, probably due to inhibition of carbonic anhydrase since similar effects were seen after acetazolamide. This effect was coupled to tubular secretion of the diuretic, and probably reflects an inhibition of carbonic anhydrase in cortical distal tubules, where the enzyme is present in the apical region of most cells and could be reached by chlorothiazide present in the tubular fluid.

Animals↗
PubMed1991

Well-being and its measurement in hypertension. A randomized, double-blind cross-over comparison of 5 mg clopamide with 25 mg hydrochlorothiazide. Hunter Hypertension Research Group.

We conducted a randomized, double-blind, cross-over comparison of six weeks' treatment with 5 mg clopamide or with 25 mg hydrochlorothiazide in 17 hypertensive patients (average age 62 years). No significant differences were found between the two treatments in blood pressure control, plasma biochemical values, body weight or response to a comprehensive "quality of life" questionnaire. Despite the apparently identical performance of both drugs, significantly (x2 = 4.76; P less than 0.05) more patients expressed a preference for clopamide (12) than for hydrochlorothiazide (3). Two had no preference. Current quality of life assessments are relatively insensitive and patient preference remains a valid discriminator between otherwise comparable medications.

Adult↗
PubMed1989

[Hemodynamic effects of hydrochlorothiazide, propranolol and a combination of pindolol and clopamide in patients with essential hypertension].

To characterize the haemodynamic effects of diuretics, betablockers and the association of both, 24 hypertensive patients, stages I-II WHO criteria, were studied. Two haemodynamic studies were performed, before under placebo and after two month of active drug therapy. Seven patients received propranolol (PPL) (160-240 mg/day); 7 patients, hydrochlorothiazide (HCT) (150-100 mg/day), and 10 a combined fixed dose of pindolol (PDL) and clopamide (CLP): PDL 10 mg, CLP 5 mg per tablet, each patient receiving one to three tablets according blood pressure response. The haemodynamic study was performed with percutaneous intravenous flow-directed. Swan-Ganz catheter, associated with direct puncture of femoral artery and measuring cardiac output by thermodilution. Arterial pressure was significantly reduced on PPL (p less than 0.05) and PDL-CLP (p less than 0.01) groups, but not in the HCT group. The cardiac index was reduced by PPL (p less than 0.05) but not by HCT and PDL-CLP. The systemic vascular resistance was only reduced in the PDL-CLP group (p less than 0.05). The use of a betablocker with intrinsic sympathetic activity (ISA) (pindolol) in association with a thiazide diuretic (clopamide) seems to induce a favourable change in systemic resistance without a deleterious change in cardiac output as occurred with propranolol.

Clopamide↗
PubMed1989

Gas-liquid chromatography-mass spectroscopy determination of clopamide in plasma.

A gas-liquid chromatography-mass spectroscopy (GLC-MS) method for the determination of clopamide (1) in human plasma was developed to evaluate the pharmacokinetics and bioavailability of 1 in humans. The method is specific, sensitive, and rapid and allows routine analysis as required for extensive pharmacokinetic studies. The assay procedure involves addition of furosemide (2) as an internal standard to plasma, separation on Sep Pack-C18 cartridges, elution by ether: methanol (1:1), evaporation, and subsequent derivatization with trimethylanilinium hydroxide in methanol (Methelute). Then, 5 microL of the reaction mixture is injected into a GLC-MS system which consists of a 1% SE-30 on Gas Chrom Q (100-120 mesh) glass column. The MS information was obtained under the following conditions: ionization beam energy 70 eV, ion source 200 degrees; and m/e 372 for single ion monitoring. The retention times for 1 and 2 were 0.6 and 1.0 min, respectively. The limit of detection is 10 ng/mL of 1 in plasma and the calibration curve was shown to be linear between 10 and 500 ng/mL of 1. After repeated analysis of spiked plasma samples, the coefficient of variation ranged from 5.1 to 8.3%. The recovery from the extraction procedure was 92 +/- 2.2%. Spiked samples frozen at -20 degrees C were stable for at least 8 weeks. The method has been successfully used in a pharmacokinetic study with po dosing of 5 mg of 1 to eight healthy volunteers. Peak plasma concentrations of 197 +/- 56 ng/mL were observed after 1.1 +/- 0.34 h. No measurable concentration of 1 beyond 12 h after dosing was observed.

Adult↗
PubMed1978

[Potassium metabolism in combined administration of pindolol and clopamide in long-term treatment of hypertension (author's transl)].

Potassium metabolism was studied in a multicentre trial of 174 out-patients with arterial hypertension of mild or moderate degree who were receiving both beta-adenergic blockers and a diuretic (1 tablet Viskaldix, containing 10 mg pindolol and 5 mg clopamide). The antihypertensive effect, heart rate and drug tolerance were also analysed. During the 15-week treatment there were no significant changes in potassium metabolism. Systolic and diastolic blood pressure, both on standing and lying, were significantly decreased, while heart rate remained within normal limits. In no instance was it necessary to discontinue the drug because it was not well tolerated.

Adult↗
PubMed1978

Treatment of hypertension in the elderly with pindolol and clopamide.

After a 2-week washout period, 30 elderly hypertensive patients were treated with pindolol (a beta-adrenergic blocker) for 3 weeks. In 13 patients the reduction in blood pressure was satisfactory and treatment with pindolol was continued for another 4 weeks. In 17 patients the subsequent treatment was supplemented with clopamide (a diuretic) for 4 weeks; in 6 the results were satisfactory. Side effects were few and mild.

Aged↗
PubMed1987

[C-alkylpiperazines. XII. Synthesis and diuretic activity of compounds structurally related to clopamide].

The synthesis and diuretic activity were reported of a series of N1-(4-chloro-3-sulfamoylbenzamide)-N4-alkylpiperazines, 2-methyl- and cis-2,6-dimethyl substituted, structurally related to clopamide, as well as of two N4-alkyl-N1-(4-chloro-3-sulfamoylbenzoyl)-2-methyl-1,2,3, 4-tetrahydroquinoxalines. In the piperazine series the presence of methyl group in position 2 and 6 of the piperazinic ring was found to increase the diuretic potency of the C-unmethylated compound.

Animals↗
PubMed1978

The influence of ethacrynic acid, hydrochlorothiazide and clopamide on the renal excretion of chloramphenicol and its metabolites.

Simultaneous administration of chloramphenicol (1 g orally) and ethacrynic acid (150 mg orally), hydrochlorothiazide (25 mg orally) or clopamide (40 mg orally) increased the urinary excretion of chloramphenicol and its metabolites (aryl amines and total nitro compounds). The administration of diuretics did not change the time course of serum concentrations of substances under study. Since the urinary excretion of chloramphenicol and its metabolites is a urine flow-dependent process, the influence of the tested diuretics can be explained as a consequence of decreased tubular water reabsorption.

Adult↗
PubMed1975

[Treatment of hypertension with a combination of prindolol and clopamide (author's transl)].

The blood pressure lowering effects of prindolol (2 x 5 mg daily) and of the combination prindolol (2 x5 mg) + clopamide (10 mg) were investigated in a single blind controlled study on 61 patients with slight hypertension and compared with placebo in another group of patients. In both groups, a significant lowering of blood pressure, both lying down and standing, could be achieved, the fall in blood pressure in standing being significantly better with the combination treatment. The number of responders was greater with the combination therapy than with prindolol alone.

Clinical Trials as Topic↗