Dose-finding study of imidapril, a novel angiotensin converting enzyme inhibitor, in patients with stable chronic heart failure

Pinto, YM; Veldhuisen, van Dirk; TjonKaJie, RT; Rooks, G; Netzer, Tilo; Lie, Ki

doi:10.1007/s002280050105

Cited by 17 publications

(10 citation statements)

References 17 publications

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“…failure have been studied mainly in adults, but these are assumed Reported pediatric experience with ACE inhibitors is limited to to be applicable in pediatric heart failure. captopril, enalapril, and cilazapril, [13] although more than ten other In heart failure, cardiac systemic output is decreased [32,33] be-ACE inhibitors have been developed and used in adults, including cause of either increased cardiac load, such as a large left-to-right alacepril, [45] benazepril, [46] delapril, [47] fosinopril, [47,48] imishunt resulting from a large ventricular septal defect in infancy, [34] dapril, [49] lisinopril, [50] perindopril, [51] quinapril, [52] ramipril, [53] or myocardial dysfunction, such as dilated cardiomyopathy temocapril, [54] and trandolapril. [55] (DCM).…”

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ACE Inhibitors in Pediatric Patients with Heart Failure

Momma

2006

Pediatric Drugs

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This article reviews reports of ACE inhibitor use in pediatric heart failure and summarizes the present implications for clinical practice. Captopril, enalapril, and cilazapril are orally active ACE inhibitors, and widely used in pediatric cardiology, although more than ten other ACE inhibitors have been applied clinically in adults. Effects of ACE inhibitors on the renin-angiotensin-aldosterone system in pediatric patients are similar to those in adults. ACE inhibitors lower aortic pressure and systemic vascular resistance, do not affect pulmonary vascular resistance significantly, and lower left atrial and right atrial pressures in pediatric patients with heart failure. In infants with a large ventricular septal defect and pulmonary hypertension, ACE inhibitors decrease left-to-right shunt in those infants with elevated systemic vascular resistance. ACE inhibitors induce a small increase in left ventricular ejection fraction, left ventricular fractional shortening, and systemic blood flow in children with left ventricular dysfunction, mitral regurgitation, and aortic regurgitation. These beneficial effects usually persist long term without the development of tolerance. Therapeutic trials of ACE inhibitors have been reported in children with heart failure and divergent hemodynamics, including myocardial dysfunction, left-to-right shunt, such as large ventricular septal defect and pulmonary hypertension, aortic or mitral regurgitation, and Fontan circulation. Hypotension and renal failure usually occur within 5 days after starting ACE inhibition or increasing the dose and, in most cases, recovery is seen after reduction or cessation of the drug. With all ACE inhibitors, smaller doses are administered initially to prevent excessive hypotension, and doses are increased gradually to the target dose. Captopril is administered orally, usually every 8 hours. Daily doses range from 0.3 to 1.5 mg/kg in children. Enalapril is administered orally, once or twice a day, and daily doses range from 0.1 to 0.5 mg/kg. Enalaprilat is administered intravenously, one to three times a day, in doses ranging from 0.01 to 0.05 mg/kg/dose. For the treatment of chronic heart failure in children, ACE inhibitors are essential along with other medications including diuretics, digoxin, and beta-blockers (beta-adrenoceptor antagonists).

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ACE Inhibitors in Pediatric Patients with Heart Failure

Momma

2006

Pediatric Drugs

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“…Imidapril is a novel ACE inhibitor without the sulfhydryl group, currently under investigation for treatment of hypertension [7, 8, 9]and heart failure [10, 11]. It is a prodrug that is converted by the liver to its active metabolite, imidaprilat.…”

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Efficacy and Safety of Imidapril in Patients with Essential Hypertension: A Double-Blind Comparison with Captopril

Huang

Chien²,

Chen³

et al. 2001

Cardiology

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In this 12-week, double-blind, parallel-group, comparative trial, 57 adult patients with mild-to-moderate hypertension were randomly allocated to receive imidapril or captopril, initially at a dose of 5 mg once a day and 25 mg twice daily, respectively. After 4 weeks of therapy, the dose of each drug was increased twice if diastolic blood pressure (DBP) remained ≧90 mm Hg. Both treatments effectively lowered DBP in a comparable manner. Mean changes from baseline in DBP at 12 weeks were –9.9 mm Hg for imidapril and –8.8 mm Hg for captopril (p = 0.488). Responder rates in patients receiving active treatment for at least 6 weeks were 53.9% for imidapril and 48% for captopril (p = 0.676). Both treatments were well tolerated. Adverse drug reactions were observed in 20.7% (6/29) of the imidapril group and 46.4% (13/28) of the captopril group (p < 0.05). A cough was the most frequent side effect, reported in 13.8% of the imidapril group and 35.7% of the captopril group. The results indicate that imidapril is as effective as captopril in the treatment of hypertension. Imidapril produces less adverse effects compared with captopril.

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“…Pinto et al (80) performed a dose-finding study to test the safety of imidapril, 2.5 mg (n = 12) and 5 mg (n = 12), in patients with clinically stable, mild-to-moderate CHF (NYHA Class II-III). He also examined the relationship between the effect of imidapril on blood pressure and inhibition of serum ACE.…”

Section: Congestive Heart Failurementioning

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Protection of the Cardiovascular System by Imidapril, a Versatile Angiotensin‐Converting Enzyme Inhibitor

Hosoya

Ishimitsu

2002

Cardiovascular Drug Reviews

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Imidapril hydrochloride (imidapril) is a long-acting, non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor, which has been used clinically in the treatment of hypertension, chronic congestive heart failure (CHF), acute myocardial infarction (AMI), and diabetic nephropathy. It has the unique advantage over other ACE inhibitors in causing a lower incidence of dry cough. After oral administration, imidapril is rapidly converted in the liver to its active metabolite imidaprilat. The plasma levels of imidaprilat gradually increase in proportion to the dose, and decline slowly. The time to reach the maximum plasma concentration (T max ) is 2.0 h for imidapril and 9.3 h for imidaprilat. The elimination half-lives (t 1/2 ) of imidapril and imidaprilat is 1.7 and 14.8 h, respectively. Imidapril and its metabolites are excreted chiefly in the urine. As an ACE inhibitor, imidaprilat is as potent as enalaprilat, an active metabolite of enalapril, and about twice as potent as captopril. In patients with hypertension, blood pressure was still decreased at 24 h after imidapril administration. The antihypertensive effect of imidapril was dose-dependent. The maximal reduction of blood pressure and plasma ACE was achieved with imidapril, 10 mg once daily, and the additional effect was not prominent with higher doses. When administered to patients with AMI, imidapril improved left ventricular ejection fraction and reduced plasma brain natriuretic peptide (BNP) levels. In patients with mild-to-moderate CHF [New York Heart Association (NYHA) functional class II-III], imidapril increased exercise time and physical working capacity and decreased plasma atrial natriuretic peptide (ANP) and BNP levels in a dose-related manner. In patients with diabetic nephropathy, imidapril decreased urinary albumin excretion. Interestingly, imidapril improved asymptomatic dysphagia in patients with a history of stroke. In the same patients it 93

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Dose-finding study of imidapril, a novel angiotensin converting enzyme inhibitor, in patients with stable chronic heart failure

Abstract: Imidapril significantly lowered systolic blood pressure and was well tolerated. The difference in the first dose response to the two doses with respect to diastolic blood pressure suggests that this haemodynamic effect of ACE-inhibition is not related to inhibition of circulating ACE.

Cited by 17 publications

References 17 publications

ACE Inhibitors in Pediatric Patients with Heart Failure

ACE Inhibitors in Pediatric Patients with Heart Failure

Efficacy and Safety of Imidapril in Patients with Essential Hypertension: A Double-Blind Comparison with Captopril

Protection of the Cardiovascular System by Imidapril, a Versatile Angiotensin‐Converting Enzyme Inhibitor

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