A study of the acute pharmacodynamic interaction of ramipril and felodipine in normotensive subjects.

Bainbridge, A. D.; Rj, MacFadyen; Lees, KR; Reid, JL

doi:10.1111/j.1365-2125.1991.tb05503.x

Cited by 20 publications

(6 citation statements)

References 23 publications

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“…Our previous acute dosing study of the combination of ramipril and felodipine ER in normotensives [26] found that the addition of ramipril attenauted the tachycardia and abolished the elevation of the heart ratesystolic pressure product attributable to felodipine ER. However, the heart rate response to felodipine resolves after about 1 week of continued treatment [27] sO it was not anticipated that heart rate changes would be found in the present study.…”

Section: Discussionmentioning

confidence: 94%

The antihypertensive efficacy and tolerability of a low dose combination of ramipril and felodipine ER in mild to moderate essential hypertension

Bainbridge

Stark

et al. 1993

Brit J Clinical Pharma

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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.

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Section: Discussionmentioning

confidence: 94%

The antihypertensive efficacy and tolerability of a low dose combination of ramipril and felodipine ER in mild to moderate essential hypertension

Bainbridge

Stark

et al. 1993

Brit J Clinical Pharma

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“…Similar reports exist that the tachycardia induced by felodipine was lessened by combined therapy with ramipril (Bainbridge et al 1991). On the other hand, many similar studies combining an ACE inhibitor with a calcium antagonist have been unable to demonstrate a significant 'buffering' effect (Donnelly et al 1986;Lees et al 1987;Pasnisi et al 1985).…”

Section: Calcium Channel Antagonistsmentioning

confidence: 57%

“…The pharmacokinetics of nifedipine were also unaltered by the addition of lisinopril (Lees & Reid 1988;Lees et al 1987). Similar studies (table IV) have reported that there are no pharmacokinetic interactions between ramipril and felodipine in 12 healthy volunteers (Bainbridge et al 1991). …”

Section: Calcium Channel Antagonistsmentioning

confidence: 73%

Pharmacokinetic Drug Interactions with ACE Inhibitors

Shionoiri

1993

Clinical Pharmacokinetics

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Angiotensin converting enzyme (ACE) inhibitors which have active moieties excreted mainly in urine require adjustment of either the dose or the interval between doses in patients with moderate to severe renal dysfunction or severe congestive heart failure. Those agents such as temocapril (CS 622) and fosinopril, excreted both in urine and bile, may not require such adjustment. Renal clearance of ACE inhibitors may be reduced and some accumulation may occur in elderly patients with mild renal dysfunction or congestive heart failure. The bioavailability of ACE inhibitors is reduced by concomitant food or antacids which may slow gastric emptying and raise gastric pH. Pharmacokinetic interactions with ACE inhibitors are unlikely in patients receiving thiazide or loop diuretics. When ACE inhibitors are given hyperkalaemia may occur in patients with renal insufficiency, those taking potassium supplements or potassium-sparing diuretics, and in diabetic patients with mild renal impairment. While no pharmacokinetic interaction precludes use of this combination, the pharmacokinetics of some ACE inhibitors are subject to greater variability when patients also receive beta-blockers. Calcium antagonists and ACE inhibitors have additive anti-hypertensive effects and pharmacokinetic interactions between these agents are unlikely. One report exists of a significant effect of coadministered hydralazine on the pharmacokinetics and urinary excretion of lisinopril. Data on interactions between ACE inhibitors and digitalis are contradictory. There is no evidence that the concomitant use of ACE inhibitors and digoxin is associated with an increased risk of digitalis toxicity. ACE inhibitors are mainly excreted by glomerular filtration and renal tubular secretion. Possible interactions between ACE inhibitors and probenecid have been noted, with renal and total body clearance of ACE inhibitors being potentially reduced in the presence of probenecid. Probenecid pretreatment may enhance the pharmacodynamic response of ACE inhibitors. Few but contradictory data exist on the effects of H2-blockers on ACE inhibitor pharmacokinetics and little information is available on interactions between ACE inhibitors and hypoglycaemic drugs. Some case reports link ACE inhibitors with the induction of lithium toxicity. Coadministration of lithium should be undertaken with caution, and frequent monitoring of lithium concentrations is recommended with all ACE inhibitors. Nonsteroidal anti-inflammatory drugs (NSAIDs) may attenuate the haemodynamic actions of ACE inhibitors. NSAIDs reduce renal excretion of ACE inhibitors, with a corresponding increase in circulating drug concentrations. There is little information available on the pharmacokinetic interaction with ACE inhibitors and cyclosporin, but caution should be employed when they are used together.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…In animals, acute felodipine administration reduces blood pressure and peripheral resistance, with acute reflex tachycardia and an increase in cardiac output, but with chronic treatment the reflex tachycardia is abolished (8), and similar changes are seen in essential hypertension (8). In healthy subjects the drug has been said to have no consistent effects on blood pressure (15) although doses as low as 1.25 mg did lower pressure in one study in normals (14) with no change in plasma renin activity, aldosterone or catecholamines (16). With chronic administration heart rate increases return to control levels (17).…”

Section: Discussionmentioning

confidence: 99%

Hemodynamic Responses to Cortisol in Man: Effects of Felodipine.

1994

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To examine the proposition that vasoconstriction is essential for onset of cortisol hypertension using the calcium channel blocking drug, felodipine. Six normal male volunteers in random order, 4 weeks apart received placebo (Study A) or 5 mg felodipine ER, orally daily (Study B) for 9 days, plus 50 mg cortisol orally, 6 hourly for 5 days, commencing day 4. Minute distance (cm/min) determinations were made using Doppler and total peripheral resistance calculated as: mean arterial pressure (MAP) (mmHg)/minute distance. There were no differences between placebo and felodipine alone (Day 1-3). On both treatments, cortisol increased blood pressure (BP), weight, white cell count, sodium and cortisol concentrations and decreased potassium, albumin, hematocrit and eosinophil count. BP was similar on both treatments. Minute distance in felodipine pre-treated subjects prior to cortisol was 1,518 ± 66 cm/min and rose with cortisol to 1,644 ± 83 cm/min (p = 0.030) but the increase in placebo pre-treated subjects was not significant. Calculated total peripheral resistance was unchanged following cortisol. Felodipine pretreatment failed to modify cortisol-induced rises in BP. An increase in peripheral resistance is not essential for production of cortisol-induced hypertension. (Hypertens Res 1994; 17: 137-142)

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A study of the acute pharmacodynamic interaction of ramipril and felodipine in normotensive subjects.

Cited by 20 publications

References 23 publications

The antihypertensive efficacy and tolerability of a low dose combination of ramipril and felodipine ER in mild to moderate essential hypertension

The antihypertensive efficacy and tolerability of a low dose combination of ramipril and felodipine ER in mild to moderate essential hypertension

Pharmacokinetic Drug Interactions with ACE Inhibitors

Hemodynamic Responses to Cortisol in Man: Effects of Felodipine.

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