Biomedical subjects

I Kobrin

Publications and source records attributed to I Kobrin.

At least 37 records · Page 2Linked to original sources

PubMed1997

Mibefradil, a novel calcium antagonist, in elderly patients with hypertension: favorable hemodynamics and pharmacokinetics.

A multicenter, double-blind, placebo-controlled study of 310 elderly patients with mild-to-moderate essential hypertension was conducted in 20 sites throughout Europe, Brazil, and Israel to assess the antihypertensive efficacy, tolerability, safety, and dose-response characteristics of the novel calcium antagonist mibefradil in the elderly. Patients were randomly assigned to receive once-daily doses of 6.25, 12.5, 25, 50, or 100 mg of mibefradil or placebo for 4 weeks. Statistically significant and clinically relevant reductions in sitting diastolic blood pressure (SDBP) and sitting systolic blood pressure (SSBP) were observed with the 50 and 100 mg doses. Therapeutic responses reached 88.5% for SDBP and 76.5% for SSBP in the 100 mg group. Trough/peak ratios were > 75% in SDBP and SSBP with the 50 mg and 100 mg doses. At doses of 50 to 100 mg once daily, mibefradil was well tolerated and effective with a high antihypertensive response rate and consistent 24-hour blood pressure control in elderly patients.

Aged↗

PubMed1997

New developments in drug therapy of hypertension.

The explosion of new knowledge about the complex mechanisms mediating high blood pressure is providing new targets for drug therapy of hypertension and other cardiovascular disorders. This article reviews the current status of several new approaches in the management of hypertension, including vasopressin antagonists, natriuretic peptide clearance inhibitors, endothelin antagonists, renin inhibitors, angiotensin receptor antagonists, and selective T-type calcium ion channel antagonists.

Animals↗

PubMed1997

Dose-response characteristics of mibefradil, a novel calcium antagonist, in the treatment of essential hypertension.

The aim of this study was to determine the dose-response characteristics of the calcium antagonist, mibefradil, and to evaluate its antihypertensive efficacy and safety in varying doses in patients with mild-to-moderate hypertension. Three hundred and three eligible patients were randomized to receive once-daily 6.25-, 12.5-, 25-, 50-, 100-, 150-, or 200-mg mibefradil doses or placebo for 4 weeks. Repeated blood pressure measurements and electrocardiographic recordings were obtained for the 24 h following the last dose of the placebo run-in period and for the first and last doses of randomized treatment. A statistically significant (P < .001 versus placebo) and clinically relevant drop in sitting diastolic blood pressure (SDBP) both at trough and at peak was observed in the 50-, 100-, 150-, and 200-mg mibefradil dose groups (trough placebo-corrected reductions: -4.9, -9.1, -9.9, and -11.9 mm Hg, respectively), with a significant dose-response relationship (P < .001) and high response rates. Trough/peak ratios for the placebo-corrected change from baseline to week 4 in SDBP were >85% for the 50- and 100-mg doses and 68% and 69% for the 150- and 200-mg doses, respectively. The full antihypertensive effect of mibefradil was achieved within 1 week of treatment. Reductions in sitting systolic blood pressure (SSBP) closely paralleled those in SDBP. The antihypertensive effect of mibefradil was associated with a slight dose-dependent decrease in heart rate and increase in the pulse rate (PR) electrocardiographic interval [corrected]. The appropriate therapeutic dose range of mibefradil in the management of mild-to-moderate essential hypertension is 50 to 100 mg.

Adolescent↗

PubMed1997

A randomised, double-blind trial comparing mibefradil and amlodipine: two long-acting calcium antagonists with similar efficacy but different tolerability profiles. Mibefradil International Study Group.

OBJECTIVE: To compare the efficacy and tolerability of mibefradil and amlodipine in patients with uncomplicated mild-to-moderate essential hypertension. DESIGN: A double-blind, randomised, parallel group multicentre trial. METHODS: 239 patients received 50 mg mibefradil or 5 mg amlodipine for 4 weeks, followed by a forced titration to 100 mg mibefradil or 10 mg amlodipine for an additional 8 weeks. Patients then entered a 4-week withdrawal period either on therapy or switched to placebo. RESULTS: Statistically equivalent reductions in trough sitting diastolic blood pressure (SDBP) were observed after 12 weeks of once-daily treatment with 50/100 mg mibefradil (-11.5 +/- 8.2 mm Hg) and 5/10 mg amlodipine (-13.2 +/- 7.9 mm Hg). The number of patients with normalised SDBP (< or = 90 mm Hg) increased 23.3% in the mibefradil group and 19.5% in the amlodipine group (approximately 74% in both groups). Patients on mibefradil or amlodipine during the withdrawal period had significantly larger decreases in SDBP than those on placebo. Patients on mibefradil had a decrease in heart rate of 5.5 bpm. Patients on amlodipine had no change in heart rate; however, cessation of amlodipine was associated with a decrease in heart rate. CONCLUSIONS: Mibefradil was as effective as amlodipine in reducing BP; both compounds were effective treatments of hypertension.

Adult↗

PubMed1997

The addition of mibefradil to chronic hydrochlorothiazide therapy in hypertensive patients is associated with a significant antihypertensive effect.

OBJECTIVE: To evaluate the antihypertensive efficacy, tolerability, safety, and dose-response characteristics of the novel calcium antagonist, mibefradil, in combination with a diuretic regimen. DESIGN: A multinational, double-blind, randomised, placebo-controlled, parallel-design trial. METHODS: Three hundred and seven patients whose mild-to-moderate essential hypertension remained uncontrolled after 4 weeks of treatment with hydrochlorothiazide (HCTZ) 25 mg/day and placebo were randomised to receive combined treatment with HCTZ and once-daily doses of 12.5, 25, 50, or 100 mg of mibefradil or placebo. After 8 weeks of combined treatment, HCTZ was withdrawn and the mibefradil groups continued on their respective doses for an additional 6 weeks. RESULTS: After 8 weeks, the addition of once-daily doses of mibefradil to the initial HCTZ regimen resulted in clinically relevant, dose-related reductions in sitting diastolic blood pressure (SDBP) and sitting systolic blood pressure (SSBP) at trough, which were significantly greater in the 50 and 100 mg dose groups compared to the placebo group (P < or = 0.003). Placebo-corrected treatment effects on SDBP and SSBP at the end of the combined treatment period relative to baseline were, respectively, -4.1 and -8.0 mm Hg in the 50 mg mibefradil group and -9.5 and -8.0 mm Hg in the 100 mg mibefradil group. Therapeutic response rates to combination mibefradil and HCTZ therapy were high and dose related, reaching 82% for SDBP in the 100 mg group. CONCLUSIONS: The addition of once-daily doses of 50 or 100 mg of mibefradil to patients whose hypertension is not controlled by HCTZ alone is well tolerated and effective in improving BP control.

Adult↗

PubMed1997

Differential properties of mibefradil in hypertension and angina.

MIBEFRADIL IN THE TREATMENT OF HYPERTENSION: The antihypertensive efficacy of mibefradil, a new selective transient (T)-channel calcium antagonist, was studied in eight randomized, double-blind, parallel-design trials: four placebo-controlled and four active drug-controlled versus other calcium antagonists. These studies established that at doses of 50 and 100 mg, mibefradil is an effective, well tolerated and safe treatment for high blood pressure. The antihypertensive effect of mibefradil was achieved gradually, with the full activity reached within 1-2 weeks. The decrease in arterial pressure was smooth and sustained over the entire 24-h dosing interval. The antihypertensive action was associated with a dose-related reduction in the heart rate. The efficacy results were similar across all demographic subpopulations studied, including high-risk groups: individuals with chronic renal failure; the elderly; and hydrochlorothiazide-treated patients. In studies comparing mibefradil with other calcium antagonists at their recommended doses, 100 mg mibefradil demonstrated significantly better antihypertensive efficacy than controlled-dose (CD) diltiazem at 360 mg or slow release (SR) nifedipine at 40 mg twice a day, and similar efficacy to that of 10 mg amlodipine or 60 mg nifedipine gastrointestinal therapeutic system (GITS). MIBEFRADIL IN THE TREATMENT OF ANGINA PECTORIS: The efficacy, safety, and tolerability of 50 and 100 mg mibefradil in the treatment of chronic stable angina pectoris was tested in six randomized parallel-design studies. Significant increases in exercise duration and a significant delay in the onset of ischemia during exercise were found in most studies with the 50-mg dose and in all studies with the 100-mg dose. Weekly anginal attacks and nitroglycerine consumption decreased significantly in a dose-related manner and, similarly, a significant dose-related decrease in the number and duration of silent ischemic episodes was observed on 48-h Holter monitoring. In the two studies with active drug controls, 100 mg mibefradil was significantly better than 10 mg amlodipine and equivalent to 120 mg diltiazem SR twice a day in improving anti-anginal and anti-ischemic parameters. In all studies, mibefradil treatment produced a dose-related reduction in the heart rate and the rate-pressure product at rest and at the end of exercise, and the magnitude of these decreases was larger than that observed with the other two calcium antagonists. SAFETY AND TOLERABILITY: An integrated analysis of combined data on the safety and tolerability of mibefradil from studies on hypertension and angina pectoris confirmed that mibefradil and diltiazem were equally well tolerated, but the incidence of leg edema was clearly higher in patients treated with the dihydropyridine calcium antagonists amlodipine and nifedipine.

Angina Pectoris↗

PubMed1996

Effects of a new calcium antagonist, mibefradil (Ro 40-5967), on silent ischemia in patients with stable chronic angina pectoris: a multicenter placebo-controlled study. The Mibefradil International Study Group.

OBJECTIVES: The purpose of this study was to evaluate the effects of mibefradil (Ro 40-5967) on the frequency and duration of episodes of asymptomatic ischemia in patients with stable angina pectoris and to determine the most efficient single therapeutic dose of this drug. BACKGROUND: Mibefradil is a novel calcium channel antagonist that shows a high bioavailability, induces no reflex tachycardia and has no negative inotropic effects. METHODS: In a multicenter, double-blind, placebo-controlled, parallel-design trial, 126 patients with chronic stable angina pectoris were studied. After 1 week of a placebo run-in period, patients were randomized to receive 25, 50, 100, 150 mg of mibefradil or placebo for 2 weeks. Ambulatory 48-h electrocardiographic (ECG) monitoring was performed at the end of both the placebo run-in period and the active treatment period. RESULTS: Compared with placebo, mibefradil was associated with significantly less ischemia as manifested during ambulatory ECG monitoring. In the 150- and 100-mg groups, respectively, the drug resulted in a 73% and 63% reduction in the frequency of episodes of ST segment depression and a 78% and 58% reduction in the total duration of ST segment depression. Highly significant linear dose-response relations were present across all treatment groups for ischemic episodes and ischemia duration (p < 0.001). Electrocardiographic abnormalities related to treatment were first-degree atrioventricular block, sinus bradycardia and short Wenckebach episodes, observed during sleep on Holter monitoring. All ECG events were dose related. CONCLUSIONS: Mibefradil is a new, safe, well tolerated and very effective dose-dependent anti-ischemic calcium channel antagonist.

Angina Pectoris↗

PubMed1996

Hemodynamic and cardiac effects of the selective T-type and L-type calcium channel blocking agent mibefradil in patients with varying degrees of left ventricular systolic dysfunction.

OBJECTIVES: This study sought to assess the hemodynamic and cardiac effects of two dose levels of mibefradil in patients with varying degrees of ischemic left ventricular dysfunction. BACKGROUND: Mibefradil is a new, selective T-type and L-type calcium channel blocking agent. Because L-type channel blockade may depress myocardial performance, an invasive hemodynamic study was performed to assess the safety of this agent. METHODS: We performed an open label study, examining the effects of two intravenous doses of mibefradil, selected to produce plasma levels comparable to those measured after oral administration of 50 mg (dose 1: 400 ng/ml) or 100 mg (dose 2: 800 ng/ml) of the drug. Variables studied included the indexes of left ventricular function and neurohormone levels. Patients were stratified according to ejection fraction (EF) (> or = 40%, n = 26; < 40%, n = 24) and the presence (n = 15) or absence (n = 35) of heart failure. RESULTS: In patients with preserved systolic function, dose 1 had no clinically significant hemodynamic effects, but dose 2 decreased mean aortic pressure and systemic vascular resistance (-8.5 mm Hg, -12%, both p < 0.01) and also reduced end-systolic stress and volume, thus improving EF (52% to 58%, p < 0.01). Heart rate tended to decrease. In patients with depressed EF, heart rate decreased significantly with both doses. The effects of dose 1 mimicked those observed after dose 2 in patients with preserved EF. Dose 2 (plasma levels 1,052 +/- 284 ng/ml) still decreased left ventricular systolic wall stress and improved EF (24.0% to 28.5%, p < 0.05) but also significantly depressed the maximal first derivative of left ventricular pressure. Examination of individual pressure-volume loops in two patients with heart failure showed a clear rightward shift of the loop despite a decrease in systolic pressure, suggesting negative inotropy. Neurohormone levels were unchanged at both dose levels and in all subgroups. CONCLUSIONS: Intravenous mibefradil was well tolerated and produced an overall favorable cardiovascular response. However, high plasma concentrations might produce myocardial depression in patients with heart failure, and caution should be exerted in this setting.

Adult↗

PubMed1996

Antihypertensive properties of the novel calcium antagonist mibefradil (Ro 40-5967): a new generation of calcium antagonists? Mibefradil International Study Group.

Preclinical and initial clinical studies suggest that the novel calcium antagonist mibefradil has a unique combination of properties. Mibefredil was evaluated in a multicenter, double-blind, placebo-controlled, parallel group trial. After 4 weeks of a placebo run-in period, 202 eligible patients with mild to moderate hypertension were randomized to receive doses of 25, 50, 100, or 150 mg mibefradil or placebo once a day for 4 weeks. Blood pressure and heart rate were measured repeatedly at trough and peak (24 and 2 to 6 hours postdose, respectively) at the end of each period. Concentration-effect relationships were evaluated at trough on the last treatment day. A significant (P<.01 versus placebo) drop in blood pressure (diastolic and systolic) was observed at trough and peak in all mibefradil groups, with a trough-peak ratio greater than 0.8, high response rate, and a significant dose-response relationship (P<.001). The full antihypertensive effect of mibefradil was achieved within 1 to 2 weeks and was associated with a slight dose-dependent decrease in heart rate and increase in PQ time. Clear dissociation was observed between the effect on blood pressure and PQ time when concentration-effect relationships were evaluated. These results indicate that mibefradil is an effective and well-tolerated antihypertensive compound at doses of 25, 50, and 100 mg once daily. The incidence of treatment-related adverse events observed in the 25-, 50-, and 100-mg dose groups was lower than in the placebo group, but it was slightly higher in the 150-mg dose group, and three patients from this group were prematurely withdrawn because of an adverse event.

Adolescent↗

PubMed1995

Effects of the new calcium antagonist mibefradil (Ro 40-5967) on exercise duration in patients with chronic stable angina pectoris: a multicenter, placebo-controlled study. Ro 40-5967 International Study Group.

Mibefradil (Ro 40-5967) is a novel calcium antagonist from a new chemical class and is the first that selectively blocks the T-type calcium channel. In this multicenter, double-blind, placebo-controlled, parallel designed study, its antianginal and antiischemic effects were evaluated in 126 patients with chronic stable angina pectoris. Exercise tests were performed after 1 week of placebo (baseline) and 2 weeks after randomization to 25, 50, 100, and 150 mg (once daily) or placebo. Highly significant dose-response relations were present across all treatment groups for exercise duration, time to angina, and time to ST-segment depression. They were associated with a dose-dependent decrease in heart rate and blood pressure and plasma concentrations > 300 ng/ml. Mibefradil was well tolerated. First-degree atrioventricular block (8%) and dizziness (7%) were the most frequently reported adverse events; however, the first-degree atrioventricular block was dose-related, and only one patient discontinued the trial because of dizziness. The excellent efficacy and adequate safety profile of mibefradil may be a consequence of T-type calcium-channel selectivity.

Adult↗

PubMed1995

Reproducibility of angiotensin converting enzyme inhibitor induced cough: a double-blind randomised study.

1. The reproducibility of angiotensin converting enzyme inhibitor induced cough was examined in a double-blind cross over study in patients previously shown to have exhibited this side effect. 2. Ninety-seven patients who had experienced angiotensin converting enzyme inhibitor cough within the last 2 years were challenged with enalapril 20 mg daily for 4 weeks to establish eligibility. Eighty-eight of 97 (91%) patients experienced a repeat of their cough symptoms. Sixty-four patients entered the double-blind part of the study where they were treated with enalapril 20 mg and a renin inhibitor for up to 4 weeks in random order. These periods were separated by a minimum 4 week placebo wash out. 3. Of 59 evaluable patients who received enalapril a second time, 37 (62.7%) experienced cough again. Of 62 patients on the renin inhibitor 16 (25.8%) experienced cough, however as it was not equi-efficacious to enalapril no valid comparison could be made. 4. Angiotensin converting enzyme inhibitor cough is not reproducible within patients, as other factors are involved in the aetiology. Objective testing with blinded assessment together with symptom reporting, would give a more accurate measure of the incidence, and mechanism of this side effect.

Adult↗

PubMed1994

Time dependency of the antihypertensive efficacy of the new renin inhibitor Ro 42-5892.

The objective of this study was to assess the antihypertensive efficacy of the new renin inhibitor Ro 42-5892 in patients with essential hypertension treated with 100 mg once daily orally. This was a double-blind, placebo-controlled, parallel group trial. After three weeks of wash-out and one week of single-blind placebo run-in periods, 25 patients with mild to moderate essential hypertension (sitting DBP between 95 and 114 mmHg) were randomised to receive either placebo (n = 12) or 100 mg of Ro 42-5892 (n = 13) once daily for eight days. On the eighth day, four hours after the oral administration, patients were randomised to receive intravenously either placebo or 10 mg of Ro 42-5892. BP and heart rate were measured repeatedly (hourly for eight hours and at the 24th hour post-dose) on the first and last days of active treatment. Compared with the placebo group, a slight decrease in sitting DBP was observed after the first dose in the Ro 42-5892 group. The decrease in sitting DBP reached significant levels only at six to eight hours post-dosing. In contrast, on the last day of active treatment, a larger, faster and longer decrease in sitting DBP was observed in the Ro 42-5892 group. Thus, the peak effect (-8.9 +/- 1.9 vs. -2.9 +/- 1.3 mmHg, P < 0.01) was reached 1.5 hours post-dosing and the trough effect (24 hours post-dosing) was slightly but significantly lower when compared with the placebo group (-3.0 +/- 1.0 vs -0.3 +/- 0.8 mmHg, P < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1993

Effects of an orally active renin inhibitor, Ro 42-5892, in patients with essential hypertension.

Ro 42-5892 (Ro) is a new renin inhibitor that has been shown to be an orally effective compound in primates and in the first exploratory studies in humans. However, no firm conclusions could be drawn from the human trials and therefore the present study was designed to evaluate the antihypertensive efficacy of the compound in a double-blind, placebo-controlled trial. After a 3 week wash-out period and a 1 week single-blind placebo period, 24 patients were randomized to receive once daily orally either placebo or 600 mg Ro 42-5892 (N = 12/group) for 8 days. On the last day of treatment, an intravenous infusion of placebo or 100 mg Ro was given in a double-blind fashion, 4 h after the oral administration. Blood pressure (BP), heart rate (HR), plasma renin activity (PRA), immunoreactive renin (IRR), and plasma Ro levels were measured repeatedly on the first and last days of treatment. After the first oral intake of Ro, sitting diastolic BP dropped significantly from 30 min to 24 h post-dose when compared to placebo (-10.2 +/- 1.2 mm Hg v - 0.4 +/- 2.0 mm Hg at peak and -6.9 +/- 1.8 mm Hg v 1.7 +/- 0.9 mm Hg at trough; P < .01 respectively). The trough effects of Ro and placebo after the 7th and 8th doses were -5.1 +/- 1.6 mm Hg v -0.2 +/- 1.0 mm Hg; P < .05 and -5.4 +/- 1.3 mm Hg v 2.3 +/- 1.2 mm Hg; P < .01, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1993

Comparison of verapamil and captopril in elderly hypertensive subjects: results of a randomized, double-blind, crossover study.

The effectiveness and tolerability of captopril and verapamil SR were compared in a double-blind, crossover study in 23 elderly hypertensives [15 males and 8 females, aged (mean +/- SEM) 68 +/- 1 years]. After 2 weeks of placebo run-in, patients were randomized to a starting dose of captopril, 12.5 mg b.i.d. or verapamil SR, 120 mg q.d. plus matched placebo of the opposite drug. Medication was titrated up over 6 weeks to a maximum dose of 75 mg of captopril or 360 mg of verapamil SR to achieve a sitting diastolic blood pressure of < 90 mm Hg. After 2 weeks of placebo washout, captopril and verapamil were crossed over. In the 20 patients who completed the study, the dose at the end of the respective treatment periods averaged 63 +/- 4 mg of captopril and 270 +/- 21 mg of verapamil SR. Blood pressure at the end of the run-in and washout placebo periods were comparable: 164 +/- 4/97 +/- 1 and 163 +/- 4/98 +/- 2 mm Hg, respectively. However, the blood pressure was significantly lower after verapamil, i.e., 147 +/- 4/86 +/- 2 mm Hg, than after captopril, i.e., 155 +/- 4/90 +/- 1 mm Hg (p < 0.05, ANOVA). There was no significant change in heart rate and laboratory parameters and no orthostatic hypotension. Captopril-treated patients reported a positive change in well being compared with placebo, although there was no overall difference between the drugs in any of the ten quality of life measurements. Three patients discontinued treatment, two because of constipation (verapamil) and one due to lack of efficacy (captopril).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1993

Multiple dose pharmacokinetics and concentration effect relationship of the orally active renin inhibitor remikiren (Ro 42-5892) in hypertensive patients.

1 Three double-blind, randomized, placebo controlled, multiple oral dose studies in patients with mild to moderate hypertension were performed to study tolerability, pharmacodynamics and pharmacokinetics of remikiren. Doses of 100-800 mg remikiren or placebo were given over 8 days to altogether 144 patient volunteers. In some cases (n = 46) single i.v. doses of 100 mg were administered 4 h after the last oral dose. Plasma remikiren concentrations, plasma renin activity and immunoreactive renin concentrations were measured. Pharmacokinetic parameters were estimated using model independent techniques and the concentration-effect relationship was evaluated using population pharmacometric methods. 2 In most patients no distinct absorption and disposition phase could be identified, since plasma concentrations fluctuated widely over a period of approximately 10 h. Peak plasma concentrations (Cmax) were achieved within 0.25-2 h postdose. Mean Cmax values (on the first and last day of oral treatment) were in the magnitude of 4-6 ng ml(-1) (200 mg), 23-27 ng ml(-1) (300 mg), 65-83 ng ml(-1) (600 mg) and 47-48 ng ml(-1) (800 mg). Cmax and AUC0-t values were clearly different for different doses within single studies. Intersubject variability in pharmacokinetic parameters was much higher than intrasubject variability. No drug accumulation in plasma was apparent. 3 Inhibition of the angiotensin I production rate correlated well with plasma drug concentrations according to the Emax-model. An IC50 value of 0.5 ng ml(-1) (0.8 nM) was estimated. No correlation between blood pressure changes on the last day of oral treatment and either plasma remikiren concentrations or plasma renin inhibition was found.

Administration, Oral↗

PubMed1991

The effect of cilazapril, a new angiotensin converting enzyme inhibitor, on peak and trough blood pressure measurements in hypertensive patients.

Cilazapril (CLZ) is a new, long-acting nonsulfhydril converting enzyme inhibitor (ACE-I). Its effect on peak and trough sitting diastolic blood pressure (SDBP) was studied in a total of 85 patients with uncomplicated, essential hypertension at three centers. After 4 weeks of a single-blind placebo (PLA) run-in period, patients whose SDBP was between 100 and 115 mm Hg, were randomized into active treatment with either PLA (n = 27), CLZ 2.5 mg (n = 29), or CLZ 5 mg (n = 29) once daily in a double-blind fashion for another 8 weeks. At the end of the PLA run-in and after 4 and 8 weeks active therapy, an hourly blood pressure (BP) profile during 1-10 and 21-24 h postdose was performed. The drop in SDBP at the end of the active treatment period at peak and trough was statistically and clinically significant for both CLZ doses in comparison with the PLA group. The peak/trough ratio after subtraction of the PLA effect was 62% for CLZ 2.5 mg and 59% for CLZ 5 mg. These results indicate that the dose regimen of CLZ 2.5-5 mg once daily is adequate and effective for 24 h.

Adult↗

PubMed1991

Improved kidney function with cilazapril in hypertensive type II diabetics with chronic renal failure.

The purpose of this study was to determine efficacy and safety of the angiotensin converting enzyme inhibitor, cilazapril, in the treatment of hypertensive diabetics with renal insufficiency. Fifteen type II diabetics with hypertension and chronic renal insufficiency aged (mean +/- SD) 64 +/- 7 years were studied in a regional clinic and university hospital hypertension unit. The blood pressure was measured biweekly. Urinary collections were done after 2 weeks of placebo and 8 weeks of cilazapril treatment. The blood pressure decreased from 176 +/- 15/105 +/- 9 to 164 +/- 11/95 +/- 9 mm Hg and serum creatinine from 197 +/- 69 to 179 +/- 73 mumol/L. The creatinine clearance rose from 41.6 +/- 11.4 to 47.4 +/- 14.9 ml/min, while protein excretion decreased from 0.8 +/- 1.3 to 0.5 +/- 0.8 g/24 h (p less than 0.05). The blood pressure change was inversely correlated with the creatinine clearance change (r = -0.5, n = 15, p less than 0.05). In these high-risk patients, 8 weeks of cilazapril treatment improved both blood pressure control and renal function but renal function improved most in the patients whose blood pressure changed the least.

Aged↗

PubMed1991

Antihypertensive duration of action of cilazapril in patients with mild to moderate essential hypertension.

The efficacy of cilazapril monotherapy was evaluated in 2 multicentre double-blind dose-response trials. After 4 weeks of a single-blind placebo run-in period, patients with uncomplicated mild to moderate essential hypertension and a sitting diastolic blood pressure of 100 to 115 mm Hg, 24 hours after the last placebo dose (trough), were randomised to take either placebo or cilazapril 2.5 mg or 5 mg for 4 weeks (study 1, 86 patients) or 8 weeks (study 2, 78 patients). Sitting diastolic blood pressure was checked every 2 weeks at trough in both studies and at peak in study 2. The reductions in sitting diastolic blood pressure from baseline at trough, and the difference from placebo, were clinically and statistically significant for both cilazapril groups in the 2 studies. The reduction in blood pressure in both active treatment groups was similar, but the response rate with cilazapril 5 mg was greater than that with 2.5 mg. More than 50% of the peak effect was still present at trough for both cilazapril groups. It is concluded that both dosages of cilazapril are effective and reduce blood pressure compared with placebo over a 24-hour period.

Adult↗