The antihypertensive efficacy and tolerability of a low dose combination of the angiotensin converting enzyme inhibitor ramipril (2.5 mg) and the extended release formulation of the dihydropyridine calcium channel antagonist felodipine (5 mg) were assessed in a double‐blind, double dummy placebo controlled, randomised, crossover study in 20 patients (mean age 55.4 years; range 46–69) with uncomplicated mild to moderate hypertension (supine diastolic >90 mmHg <115 mmHg after 4 weeks of single‐blind wash‐out on placebo). The four randomised, double‐blind, crossover study phases evaluated the response to 4 weeks of once daily treatment with placebo, monotherapy with each drug and the combination. Noninvasive ambulatory blood pressure monitoring (Spacelabs 90207) was performed for 24 h at the end of each phase. The mean 24 h ambulatory blood pressure (mmHg) was 147.9/92.0 following placebo, 141.3/87.8 following monotherapy with ramipril 2.5 mg, 136.8/85.8 following monotherapy with felodipine ER 5 mg and 131.1/82.6 following the combination of ramipril 2.5 mg and felodipine ER 5 mg. All active treatment phases significantly reduced mean 24 h ambulatory diastolic pressure by comparison with placebo. The antihypertensive efficacy of the combination was additive. The coadministration of ramipril did not attenuate the incidence of headache attributable to felodipine ER.

This study investigated potential therapeutic differences between Amlodipine 5 mg and Felodipine ER 10 mg in 12 normotensive/borderline hypertensive subjects by comparison of the plasma drug concentration-time profiles and the blood pressure and heart rate responses. There was significantly less trough-to-peak variability in plasma drug concentrations with amlodipine with a ratio of 67%, compared to 37% for felodipine. Correspondingly there was less variability with amlodipine in the blood pressure reductions across the dosage interval. Overall, amlodipine displayed a more consistent hypotensive effect across 24 hours and lower blood pressure values at trough, i.e. 24 hours post-dose.

1. The possibility of an acute pharmacokinetic or pharmacodynamic interaction between the ACE inhibitor ramipril and the calcium antagonist felodipine was examined in 12 normotensive male volunteers. 2. Ramipril (5 mg) and felodipine ER (10 mg) were administered orally in a double‐blind, randomised, placebo‐controlled, Latin square design to fasting subjects. 3. There was no evidence of a pharmacokinetic interaction between agents. The concentration‐time profiles remained unaltered by coadministration of both agents. 4. Plasma ACE inhibition by ramiprilat was unaffected by concurrent felodipine. The trend towards increased fractional sodium excretion after felodipine was not influenced by ramipril. Plasma renin activity, aldosterone and catecholamines remained unaltered. 5. Combination therapy produced a statistically significant fall in blood pressure supine and erect which was not evident with monotherapy. The reflex tachycardia associated with felodipine monotherapy was significantly attenuated by the coadministration of ramipril. 6. This study presents further evidence for the effective combination of ACE inhibitors and calcium antagonists to lower blood pressure. The reflex tachycardia associated with calcium antagonist therapy can be significantly reduced by coadministration with sustained antihypertensive effect.

1 The importance of total dose to the initial hypotensive response with an angiotensin converting enzyme inhibitor (quinapril) was assessed using a suggested 'maintenance' dose (20 mg) 27 patients entered a double-blind, randomised, crossover study of quinapril or placebo using ambulatory monitoring to assess BP response. 4 All patients remained asymptomatic and both therapy and monitoring were well tolerated. A smooth onset of antihypertensive effect was noted with an overall 24 h placebo corrected fall in systolic BP of 9.9 mmHg (7.2 -12.6 95 % CI) and diastolic BP of 6.4 mmHg (4.2-8.8) with no significant effect on heart rate. Individual placebo corrected maximal responses during the first 8 h following quinapril showed a wide range for both systolic (+1.56 to 44.0 mmHg) and diastolic (+2.3 to -35.6 mmHg) pressure. Larger falls tended to be associated with higher baseline pretreatment pressures but in no case did absolute systolic pressure fall below 100 mmHg during the first 8 h following administration of placebo or quinapril. In this relatively small study blood pressure responses were not correlated either to pretreatment plasma renin or starting blood pressure. 5 This study suggests that in uncomplicated hypertension, in the absence of sodium or volume depletion or other predisposing conditions such as cardiac failure, an excessive fall in blood pressure is unlikely to occur and therefore dosage reduction is probably unnecessary.Keywords first dose hypotension ACE inhibition quinapril essential hypertension ambulatory blood pressure recording

No abstract