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.
Subject(s)
Hypertension/drug therapy , Proline/analogs & derivatives , Antihypertensive Agents/therapeutic use , Blood Pressure , Chlorthalidone/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Female , Fosinopril , Humans , Hypertension/physiopathology , Male , Proline/administration & dosage , Proline/adverse effects , Proline/therapeutic use , Supination , Time FactorsABSTRACT
The pharmacokinetics, efficacy, and safety of nadolol were evaluated in hypertensive patients maintained on long-term hemodialysis. In nine patients the plasma elimination half-life of unchanged nadolol averaged 26 hours following a single 40 mg oral dose during the interdialytic period. Nineteen patients received nadolol once after each dialysis session. In addition, 12 of the 19 patients also received hydralazine and/or furosemide daily. Predialysis blood pressures and heart rates were significantly lower with nadolol than with combination or single therapy with conventional antihypertensive drugs, including other beta blockers. Nadolol administered only after each dialysis session (i.e., two or three times a week), in conjunction with hydralazine and/or furosemide, is an effective antihypertensive agent in hypertensive patients receiving long-term hemodialysis.
