Trough:peak ratio of nifedipine gastrointestinal therapeutic system and nifedipine retard in essential hypertensive patients: an Italian multicentre study.

OBJECTIVE: To evaluate the antihypertensive effect of nifedipine gastrointestinal therapeutic system and retard in terms of trough:peak ratio efficacy. METHODS: According to a double-blind, randomized, crossover design, 58 patients with mild-to-moderate essential hypertension, after 1 month placebo washout, received 30 mg/day nifedipine gastrointestinal therapeutic system, 20 mg nifedipine retard twice a day and the corresponding placebos for 1 month. At the end of each treatment period, blood pressure was measured by using a mercury sphygmomanometer at trough and 1, 2, 3 and 4 h after the last dosing. The peak effect was identified as the maximum decrement induced by the three randomized treatments with respect to the value at the end of the placebo washout period during the 4 h interval. The trough:peak ratios of systolic and diastolic blood pressure were calculated as group ratios and individual ratios from decrements induced by nifedipine gastrointestinal therapeutic system and retard, corrected for those induced by randomized placebo. Patients were defined as responders to each randomized treatment if their diastolic blood pressure at trough time was reduced by at least 10 mmHg relative to that at the corresponding time at the end of placebo washout. RESULTS: Nifedipine gastrointestinal therapeutic system and retard significantly reduced blood pressure to a similar extent both at trough and at peak. Systolic and diastolic group trough:peak ratios in responders to nifedipine gastrointestinal therapeutic system (n = 41) were 0.80 and 0.88, respectively, and those in responders to nifedipine retard (n = 30) 0.84 and 0.93, respectively. The percentage of patients with trough:peak ratios > 0.50 was > 80% (systolic trough:peak ratios) and above 90% (diastolic trough: peak ratios) for both nifedipine formulations. CONCLUSIONS: Our data show that 30 mg/day nifedipine gastrointestinal therapeutic system and 20 mg nifedipine retard twice a day have a favourable trough:peak ratios efficacy when given as monotherapy to essential hypertensive patients.

Antihypertensive effect of once daily sustained release isradipine: a placebo controlled cross-over study.

To evaluate the magnitude and duration of the antihypertensive effect of sustained release (SRO) isradipine, 37 uncomplicated essential hypertensive patients (diastolic blood pressure 100-115 mm Hg after a one month run-in on placebo) were randomised to receive, according to a double-blind cross-over design, isradipine SRO 5 mg once daily and the corresponding placebo for 1 month. At the end of each treatment period, sitting blood pressure and heart rate were measured immediately before and every hour for 6 h after the last dose. Thirty-four patients [16 m, age 54 (7) y] completed the study. As compared to randomised placebo, isradipine SRO significantly reduced the systolic (SBP) and diastolic (DBP) blood pressure. Absolute DBP decrements versus placebo peaked 6 h after dosing (-8.8 mm Hg) and were not significantly lower (-8.2 mm Hg) at the end of the dose interval. At the same times, the absolute decrements in SBP were -9.8 mm Hg and -9.7 mm Hg, respectively. DBP was normalised in 19 patients (56%) at peak and in 17 (50%) at trough time. The trough to peak efficacy ratio in patients with peak DBP < or = 90 mm Hg was 70%. Heart rate was slightly increased by isradipine SRO. Adverse effects monitored with a check-list occurred in 8/36 patients (22%) on isradipine SRO and in 4/35 (11%) on randomized placebo. The data suggest that isradipine SRO is an effective antihypertensive drug, with a trough to peak efficacy ratio supporting once daily administration in most mild to moderate essential hypertensives.

The combination of chlorthalidone with nifedipine does not exert an additive antihypertensive effect in essential hypertensives: a crossover multicenter study.

To evaluate whether the combination of nifedipine with chlorthalidone exerts an additive antihypertensive effect when compared to single-drug treatment, 66 uncomplicated essential hypertensives, whose diastolic blood pressure was greater than 100 and less than 115 mm Hg at the end of a 1-month washout placebo period, received, according to a randomized, double-blind, crossover design, nifedipine (20 mg b.i.d.), chlorthalidone (25 mg o.d.), the two drugs combined at the same doses, and the corresponding placebo. When compared to the randomized placebo the three active treatments significantly (p less than 0.001) reduced blood pressure without changing heart rate and body weight. However, blood pressure values were similarly reduced under nifedipine and the combination and were significantly lower (p less than 0.05) than those under chlorthalidone. Moreover, the percentage of responders and normalized patients under nifedipine and the two drugs combined were similar and significantly (normalized, p less than 0.0001; responders, p less than 0.02) greater than those under chlorthalidone. Under chlorthalidone and its combination with nifedipine, plasma potassium tended to decrease and blood glucose and serum uric acid were significantly (p less than 0.05) increased. These data show that the combination of nifedipine with chlorthalidone does not exert any additive antihypertensive effect when compared to nifedipine alone and that this combination increases both blood glucose and serum uric acid. Taken together these findings indicate that the combination of a dihydropyridine calcium antagonist with a thiazide diuretic is devoid of any clinical significance in the treatment of uncomplicated essential hypertensives.

Chlorthalidone does not increase the hypotensive effect of nifedipine in essential hypertensives: a crossover multicentre study.

To determine whether the combination of nifedipine + chlorthalidone exerts an additive antihypertensive effect when compared with single-drug treatment, we studied 66 uncomplicated essential hypertensives, with diastolic blood pressure of greater than 100 and less than 115 mmHg. At the end of a 1-month washout placebo period, using a double-blind crossover design, the patients were randomly allocated to nifedipine (20 mg twice a day), chlorthalidone (25 mg once a day), the two drugs combined at the same doses and the corresponding placebo. Compared with the randomly allocated placebo, the three active treatments significantly reduced blood pressure without changing the heart rate or body weight. Both the absolute and percentage decreases in mean blood pressure induced by nifedipine and the combination compared with placebo were similar and significantly greater than those induced by chlorthalidone. Taken together, these data show that the combination of nifedipine + chlorthalidone does not exert any additive antihypertensive effect compared with nifedipine alone. This finding indicates that the combination of a dihydropyridine calcium antagonist + a thiazide diuretic is probably devoid of any particular clinical significance in the treatment of uncomplicated essential hypertensives.