Once-daily fosinopril in the treatment of hypertension.

Abstract

This multicenter, dose-ranging study evaluated the antihypertensive effectiveness of once-daily administration of fosinopril sodium in 220 patients with supine diastolic blood pressure of 95-115 mm Hg. After a 4-week placebo period, patients were randomly assigned to double-blind therapy with either placebo or 10, 40, or 80 mg fosinopril once daily for 4 weeks. If treatment goals were not met, chlorthalidone 25 mg/day was added for weeks 5 to 8. Thereafter, patients could enter the long-term, open-label phase and receive 10-80 mg/day fosinopril plus chlorthalidone, if needed. After 4 weeks of monotherapy, the average decreases in supine diastolic blood pressure were 9% (10 mg), 11.5% (40 mg), and 12.5% (80 mg) compared with 6% in the placebo group. After 8 weeks, the average decreases, with or without diuretic therapy, were 12.5-18.2%, compared with 10.8% with placebo. Blood pressure continued to be well controlled, and the patients showed no evidence of tachyphylaxis or tolerance through 12-15 months of treatment Fosinopril was well tolerated. During the short-term phase, no patient withdrew because of adverse events possibly related to fosinopril; during the long-term phase, nine of 148 patients (6.1%) withdrew for that reason. In patients with mild-to-moderate hypertension, once-daily fosinopril (40 and 80 mg) provided significant antihypertensive effects with or without diuretic therapy. The 10 mg dose was effective in some patients and may be considered a starting dose. (Hypertension 1991;17:636-642)

Is the Extrapolated Adult Dose of Fosinopril Safe and Effective in Treating Hypertensive Children?

“…The 10-mg dose is not consistently different from placebo. 12 In this study, the absence of a dose-response effect in children could be because there is no such effect or because all doses were too high. In the withdrawal phase, the placebo group had greater SBP increases than the fosinopril group, indicating all 3 fosinopril doses were effective in reducing SBP.…”

“…The proportional contrast coefficients used to determine sample size for the dose-response phase assumed that the true response in SBP is linear in dose and differs by 6.0 mm Hg between the high and low doses with a standard deviation of 12 mm Hg. 12 A sample size of 62 subjects per dose level provides 80% power to detect a change from baseline in SBP across the 3 dose regimens with a 2-sided test of contrast at the 0.05 level.…”

Fosinopril: Emerging Considerations and Implications for Angiotensin‐Converting Enzyme Inhibitor Therapy

“…No. 4,1998 captopril and fosinopril half-lives is a probable explanation for the differing duration of action of these compounds. For example, 24 h after administration of placebo, captopril, or fosinopril to conscious rats, an angiotensin I infusion increased mean arterial pressure (MAP) 44 A 1 mm Hg in captopril-treated animals and only 22 ?…”

“…Single and multiple-dose fosinopril, with (4,44,74,89,111) or without (4,14,36,44,89) concomitant diuretic therapy, effectively lowers MAP in humans as well as in a number of animal models of hypertension (Table 2) (77,82). The onset of action of fosinopril is gradual and sustained over 24 h (37,79), and long-term treatment is not accompanied by tachyphylaxis (4). The greatest reduction in blood pressure occurs within 3 to 6 h after administration (4,33), and approximates the time to peak blood levels of fosinoprilat (92).…”

ACE Inhibitors

“…ACE inhibitor-induced reduction in BP is related to plasma concentrations of the active drug and not the dose of the drug, although, in general, higher doses produce greater reduction in BP than lower doses, [144] For many ACE inhibitors, increasing the dose beyond a certain level has no additional BP lowering effect, but it does prolong the duration of effect. [I 45, 146] There is no correlation between the antihypertensive efficacy of ACE inhibitors and the age of patients, Reduced renal function results in increased plasma concentrations and areas under the plasma concentration vs time curve (AUC) of active drugs and metabolites which are primarily excreted by the kidney, Hence, dosages of most ACE inhibitors should be adjusted according to renal function (table V) [136,137,[147][148][149] and actual response, and not according to the age of the patient.…”