Biology of a novel class of potent long-acting angiotensin converting enzyme inhibitors

DeForrest, Jack M.; Waldron, Thomas L.; Scalese, Robert J.; Harvey, Charlotte

doi:10.1097/00004872-198812040-00148

Journal of Hypertension

1988

DOI: 10.1097/00004872-198812040-00148

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Biology of a novel class of potent long-acting angiotensin converting enzyme inhibitors

Jack M. DeForrest¹,

Thomas L. Waldron²,

Robert J. Scalese³

et al.

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1994

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“…Fosinopril, a phosphinic acid derivative, is a member of a new class of ACE inhibitors with long-lasting action, allowing once-dairy dosing. 1 Being a prodrug, fosinopril needs to be hydroryzed into fosinoprilat, the active form, at the liver and, while absorbed, at the intestinal mucosa. It is 95% to 99% protein bound in the systemic circulation.…”

mentioning

confidence: 99%

Combined versus single effect of fosinopril and hydrochlorothiazide in hypertensive patients.

Fernández

Madero²,

González³

et al. 1994

Hypertension

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The antihypertensive effect and safety of fosinopril and hydrochlorothiazide combined were compared with each drug singly and placebo in a controlled manner. After a 4-to 5-week placebo lead-in period, 67 mild to moderate essential hypertensive patients (seated diastolic blood pressure £95 and £110 mm Hg) were randomized in a double-blind fashion into four parallel treatment groups: 20 mg fosinopril plus 12.5 mg hydrochlorothiazide, 20 mg fosinopril, 12.5 mg hydrochlorothiazide, and placebo during 8 weeks. Patients were seen biweekly. Sitting diastolic blood pressure was the outcome variable defining therapeutic response. The efficacy of fosinopril plus hydrochlorothiazide as a combined therapy was superior to any single drug (P<.05) and placebo (P<.01) in the treatment of mild to moderate essential hypertension. Mean adjusted systolic/diastolic blood pressure decrements at week 8 were -18.8 /-13.7, -12.9/-11.8, -8.5/-9.3, and -2.11-6.9 mm Hg for the fosinopril plus hydrochlorothiazide, fosinopril, hydrochlorothiazide, and placebo groups, respectively. Clinical adverse events and laboratory changes documented throughout the study were similar to placebo and were mild in severity in all groups. 1 Being a prodrug, fosinopril needs to be hydroryzed into fosinoprilat, the active form, at the liver and, while absorbed, at the intestinal mucosa. It is 95% to 99% protein bound in the systemic circulation. Elimination is evenly divided between hepatic and renal routes, 2 a favorable pattern when diseases of either organ exist. 34 Fosinopril has been administered in doses ranging from 10 to 40 mg once daily. 5 Hydrochlorothiazide, a widely used antihypertensive thiazide diuretic, enhances sodium and chloride excretion. Its diuretic effect is associated with moderate potassium and bicarbonate losses, lipid and carbohydrate metabolism alterations, and hyperuricemia.Combining an ACE inhibitor and diuretic is common in clinical practice because of their additive antihypertensive effects. When antihypertensive agents with different mechanisms of action are given in combination, in many patients the effective dose of each is smaller than the effective dose of each agent if given alone; the lower doses minimize the potential for dose-dependent adverse events.6 Furthermore, ACE inhibitors may blunt some of the adverse metabolic effects of thiazides, including hypokalemia. The purpose of the present study was to compare the safety and efficacy of the aggregate, once-daily administration of 20 mg fosinopril plus 12.5 mg hydrochlorothiazide against each drug singly and placebo in the treatment of patients with mild to moderate essential hypertension. MethodsMen and nonpregnant, nonlactating women 18 to 75 years of age with mild to moderate essential hypertension (defined as seated diastolic blood pressure [SeDBP] 2:95 and £110 mmHg) at two major referral centers in Mexico City were candidates for the study. Patient recruitment started after observers were trained and standardized at each center, and a written consent was...

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mentioning

confidence: 99%

Combined versus single effect of fosinopril and hydrochlorothiazide in hypertensive patients.

Fernández

Madero²,

González³

et al. 1994

Hypertension

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Biology of a novel class of potent long-acting angiotensin converting enzyme inhibitors

Cited by 1 publication

References 0 publications

Combined versus single effect of fosinopril and hydrochlorothiazide in hypertensive patients.

Combined versus single effect of fosinopril and hydrochlorothiazide in hypertensive patients.

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