The efficacy and safety of once-daily nifedipine administered without food: the coat-core formulation compared with the gastrointestinal therapeutic system formulation in patients with mild-to-moderate hypertension. Nifedipine Study Group.

A parallel-group, randomized, double-blind, forced-titration, multicenter study was done to compare the efficacy and safety of once-daily nifedipine coat-core (NIF CC) and once-daily nifedipine gastrointestinal therapeutic system (NIF GITS) dosed in the fasting state in patients with mild-to-moderate essential hypertension. Both formulations have been shown to effectively and safely lower blood pressure in placebo-controlled trials. After a 4-week placebo run-in period, 228 patients were randomized to 4 weeks of treatment with either NIF CC 30 mg daily or NIF GITS 30 mg daily. This period was followed by a forced-titration period to nifedipine 60 mg daily for an additional 4 weeks of double-blind therapy. After the 30-mg treatment period (the primary time point), there were no statistically significant differences between treatment groups in mean change from baseline in trough supine diastolic blood pressure, the primary efficacy variable (NIF CC patients, -7.0 mm Hg; NIF GITS patients, -8.4 mm Hg; P = 0.139). Also, because the upper bound of the treatment difference confidence interval was < 3.0 mm Hg, equivalence--as defined in the protocol--was established. After the 60-mg treatment period, the change from baseline in trough supine diastolic blood pressure was significantly greater for patients treated with NIF GITS than for patients treated with NIF CC (NIF GITS patients, -12.0 mm Hg; NIF CC patients, -8.4 mm Hg; P < 0.001). Because the upper bound of the confidence interval was > 3 mm Hg, equivalence cannot be claimed. No statistically significant differences were noted for the comparison of mean 24-hour ambulatory blood pressure monitoring changes. Both formulations were well tolerated.

The efficacy and safety of once-daily nifedipine: the coat-core formulation compared with the gastrointestinal therapeutic system formulation in patients with mild-to-moderate diastolic hypertension. Nifedipine Study Group.

The efficacy and safety of two sustained-release formulations of nifedipine, the coat-core system (NIF CC) and the gastrointestinal therapeutic system (NIF GITS), were examined in 228 patients with mild-to-moderate essential hypertension in this 16-week, multicenter, randomized, double-blind study. The coadministration of food affects the nifedipine pharmacokinetics with differing magnitudes for the two formulations. To evaluate drug safety under the most rigorous circumstances, all medication was given with food. After a 4-week placebo lead-in period, eligible patients were randomized to a parallel-group treatment period of either NIF CC or NIF GITS. 30 mg daily with food for 4 weeks, followed by forced titration to nifedipine 60 mg daily for an additional 4 weeks. For the final 4-week period, half of the patients receiving each formulation were switched to the alternate formulation at a dose of 60 mg daily. Within treatment groups, all four blood pressure variables (systolic and diastolic measurements for both trough and 24-hour periods) demonstrated significant reductions (P < 0.05) from baseline (established after the placebo lead-in period) for both formulations at every subsequent visit and end point. When comparing the two formulations, the mean change from baseline in 24-hour systolic and diastolic blood pressure measurements, determined by using ambulatory monitoring, was not statistically different for both doses (P > 0.05). The mean change in trough blood pressure from baseline during the parallel-group treatment period was statistically significant in favor of NIF GITS for both the 30-mg and 60-mg doses (P < 0.05). The treatment-emergent adverse-event rates for both formulations were similar during the parallel-group period, with the exception of dizziness, which was higher for patients receiving NIF CC. Both formulations were well tolerated and reduced blood pressure over the 24-hour dosing interval even when coadministered with food. When half of the patients receiving NIF GITS 60 mg daily were randomly crossed over to NIF CC 60 mg daily, there were no significant changes in either the trough or 24-hour mean blood pressure measurements (P > 0.05), adverse events, or dropout rates. When patients receiving NIF CC 60 mg were crossed over to NIF GITS 60 mg daily, they exhibited no significant change in diastolic blood pressure (P > 0.05). This study demonstrated that when given with food, both NIF CC and NIF GITS reduce 24-hour mean blood pressure measurements similarly.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of amlodipine on ambulatory blood pressure in hypertensive patients.

Certain high-risk populations, such as diabetics and blacks, have sustained elevation in blood pressure and heart rate throughout the day and night, with blunting of the usual diurnal variability pattern. This may contribute to their higher incidence of left ventricular hypertrophy (blacks) and cardiovascular complications (diabetics). Hypertensives who maintain a diurnal pattern of blood pressure variation still exhibit higher daytime and nocturnal blood pressure levels than normotensives. Thus, to achieve maximum effectiveness in treating hypertension, 24-hour control of blood pressure is necessary. Antihypertensive agents should effectively reduce blood pressure consistently throughout a 24-hour period. The objective of this study was to assess the effects of amlodipine, 5 mg once daily, on blood pressure measured by 24-hour ambulatory monitoring in a randomized, double-blind, placebo-controlled single-site study. Patients with mild-to-moderate essential hypertension were randomized to receive amlodipine (n = 11) or placebo (n = 5) in a 2:1 ratio. A 4-week single-blind placebo run-in period was followed by a 4-week double-blind phase. Ambulatory monitoring of blood pressure was carried out for 24 hours at the end of each 4-week phase. Patients receiving amlodipine had significantly lower blood pressure compared with placebo 24 hours after the last dose (supine blood pressure -25.1/-10.1 mm Hg; standing blood pressure -21.2/-9.7 mm Hg) after 4 weeks of treatment. This effect was clearly demonstrated by the 24-hour postdose measurement and the mean blood pressure over the 24-hour interval as measured by ambulatory recordings.(ABSTRACT TRUNCATED AT 250 WORDS)

Pentoxifylline in the treatment of vascular impotence--case reports.

Vascular impotence is a common medical problem for which available therapies are limited. Three impotent patients observed in the authors' practice who were receiving pentoxifylline for treatment of claudication of the lower extremities spontaneously reported improved sexual function. A controlled trial of pentoxifylline for vascular impotence may be warranted.

Effect of amlodipine on 24-hour ambulatory blood pressure in hypertensive patients.

Sixteen hypertensive patients (diastolic blood pressure of 95-114 mm Hg) were randomized to receive 5 mg of amlodipine daily or placebo, double blind, for 4 weeks. Antihypertensive efficacy was assessed using ambulatory blood pressure monitoring at baseline and following double-blind therapy in conjunction with sphygmomanometric measurement at 2-week intervals. Laboratory tests, ECG, and adverse effects were recorded to assess tolerability. Amlodipine treatment significantly reduced ambulatory blood pressure without altering the normal circadian variation throughout the monitoring period. Supine and standing blood pressure were significantly reduced by amlodipine 24 h postdose. Amlodipine was well tolerated and was not associated with reflex tachycardia.

Nitrendipine in severe hypertension. Satellite symposium on calcium antagonists.

We report the results of a multicenter trial in which nitrendipine, alone or in combination with a diuretic, a beta-blocker, or both, was administered to 114 patients with severe hypertension (greater than or equal to 115 mm Hg). Nitrendipine was titrated in doses of 5 to 30 mg b.i.d. If blood pressure was not controlled with nitrendipine alone, hydrochlorothiazide or propranolol or both were added. After a mean of 29 days in the study, 96 (90%) of 107 patients reached the initial goal of therapy; in 44 (41%) given nitrendipine alone the mean decrease in supine blood pressure was 38/25 mm Hg. After a mean of 91 days, 69 (72%) of 96 patients achieved the final goal of therapy; in 24 (25%) patients given nitrendipine alone the mean supine blood pressure decrease from baseline was 49/33 mm Hg. Falls in blood pressure were comparable in the patients given drug combinations. Seventy-two of 114 patients given study drug(s) had adverse experiences; headache and edema were the most frequent complaints. Only four patients dropped out of the study because of adverse effects. Most abnormal laboratory values occurred when nitrendipine was given with hydrochlorothiazide or propranolol or both. Analysis of severely hypertensive patients followed up in our Virginia center revealed continued control of blood pressure after long-term follow-up (43 +/- 3 [SD] months). Average supine blood pressure was reduced from 180/121 +/- 21/5 to 140/90 +/- 16/9 (SD) mm Hg (p less than 0.001). It was concluded that the calcium antagonist nitrendipine, alone or in combination with a diuretic or beta-blocker or both, is effective in the treatment of severe hypertension.

A double-blind evaluation of the effect of amlodipine on ambulatory blood pressure in hypertensive patients.

Amlodipine is a new long-acting calcium antagonist that has a long half-life and appears to be suitable for once-daily administration. A double-blind, randomized, parallel, placebo-controlled study was conducted to evaluate the effect of amlodipine on ambulatory blood pressures in hypertensive patients. The study consisted of a 4-week single-blind placebo run-in phase, followed by 4 weeks of double-blind therapy. Ambulatory blood pressure was measured for 24 h at the end of the placebo run-in phase and after double-blind therapy. Sixteen patients were randomized to receive either amlodipine 5 mg or placebo in a 2:1 ratio. Amlodipine 5 mg daily significantly reduced supine and standing blood pressure 24 h postdose. Ambulatory blood pressure recordings revealed adequate blood pressure control throughout the 24-h dosing interval. Amlodipine was well tolerated and only two patients reported side effects--neither was withdrawn from therapy. No treatment-related abnormalities were noted. It was concluded that amlodipine 5 mg daily was effective antihypertensive therapy throughout the 24-h dosing period in the patients studied, and it was well tolerated.