Pharmacokinetics, Safety, and Tolerability of the Novel Oral Direct Renin Inhibitor Aliskiren in Elderly Healthy Subjects

Vaidyanathan, Sujata; Reynolds, Christine; Yeh, Ching-Ming; Bizot, Marie-Noelle; Dieterich, H. A.; Howard, David L.; Dole, William P.

doi:10.1177/0091270006297921

Cited by 49 publications

(31 citation statements)

References 34 publications

(39 reference statements)

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“…Although the AGELESS study was the first prospective study in that regard, a number of studies of aliskiren included elderly patients for whom the drug provided BP reduction and was well tolerated. 20,26,27 Two previous trials have compared aliskiren with ramipril. One study assessed the effects of aliskiren compared with ramipril or the agents combined for 8 weeks in patients with diabetes and hypertension.…”

Section: Discussionmentioning

confidence: 99%

Aliskiren for Geriatric Lowering of Systolic Hypertension: a randomized controlled trial

et al. 2009

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Efficacy and safety of the direct renin inhibitor aliskiren was compared with ramipril for treatment of essential systolic hypertension in elderly patients. A 36-week, randomized, double-blind, parallel-group, active-controlled, optional-titration study was performed in 901 patients (aliskiren, n ¼ 457; ramipril, n ¼ 444) X65 years of age with systolic blood pressure (SBP) X140 mm Hg. Aliskiren 150-300 mg per day or ramipril 5-10 mg per day for was administered for 12 weeks with optional add-on therapy of hydrochlorothiazide (12.5-25 mg per day) at week 12 and amlodipine (5-10 mg per day) at week 22. The primary end point was non-inferiority of aliskiren vs ramipril monotherapy for change from baseline in mean sitting SBP (msSBP) at week 12. Decreases from baseline msSBP and mean sitting diastolic BP with aliskiren monotherapy (À14.0 and À5.1 mm Hg, respectively) were non-inferior (Po0.001 for both values) and superior to ramipril monotherapy (À11.6, À3.6 mm Hg; P ¼ 0.02, Po0.01, respectively). More patients achieved BP control with aliskiren (42%) than ramipril (33%; Po0.01). At week 36, fewer patients receiving aliskiren-based therapy required add-on treatment with hydrochlorothiazide or amlodipine (P ¼ 0.01 and 0.048, respectively). Tolerability was similar, but more patients receiving ramipril reported cough (Po0.001). In elderly patients with systolic hypertension, aliskiren proved to be more effective and better overall anti-hypertensive therapy compared to ramipril.

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Section: Discussionmentioning

confidence: 99%

Aliskiren for Geriatric Lowering of Systolic Hypertension: a randomized controlled trial

et al. 2009

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“…In particular, both drugs have a negligible renal clearance - they are both cleared exclusively by the liver and are undergoing possible enterohepatic recycling. Furthermore, following a single 300-mg oral dose of aliskiren, the increase in exposure observed in elderly subjects as opposed to a younger population [15] is comparable to that observed with ACT-077825. …”

Section: Discussionmentioning

confidence: 99%

Single-Dose Pharmacokinetics of the Renin Inhibitor ACT-077825 in Elderly and Young Subjects of Both Sexes

2014

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Background/Aims: The study objective was to investigate and compare the pharmacokinetics of a single oral dose of ACT-077825, a novel direct renin inhibitor, in young and elderly, male and female healthy subjects and to evaluate the safety and tolerability of ACT-077825 in these population groups. Methods: A total of 32 healthy subjects were included in this single-center, open-label study. The subjects were divided into 4 groups, including 8 young male, 8 young female, 8 elderly male and 8 elderly female subjects. Each participant received a single 200-mg dose of ACT-077825. Blood samples were taken over 5 days (120 h) to determine the plasma levels of ACT-077825. Safety and tolerability were monitored using standard assessments before drug administration, on the administration day and at the end of the blood sampling period. Results: Upon pooling male and female subjects, exposure was higher in elderly compared to young subjects, showing an increase of 65% for AUC_0-_∞, 40% for C_max and 38% for t_1/2. While young male and female subjects showed similar plasma profiles and exposure, a significant increase in exposure occurred with age in both sexes compared to younger subjects. The difference was largest between young and elderly females. Furthermore, the exposure to ACT-077825 was around 30% higher in elderly female compared to elderly male subjects. ACT-077825 was well tolerated by all groups, including the elderly females who showed the highest exposure. Conclusions: ACT-077825 exposure is moderately increased in elderly subjects. The clinical relevance of this observation should be explored in the context of further studies.

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“…Aliskiren exerts an antihypertensive effect that is independent of the serum renin activity, and it is possible to obtain an adequate antihypertensive effect even in the elderly (17). Moreover, higher blood aliskiren concentrations have been reported to be maintained in the elderly compare with younger people (18). If the increases in aliskiren concentrations in the blood and antihypertensive effects are proportional, then that may explain the higher target BP achievement rate observed in the elderly patients.…”

Section: Discussionmentioning

confidence: 99%

Antihypertensive Efficacy of the Direct Renin Inhibitor Aliskiren as Add-on Therapy in Patients with Poorly Controlled Hypertension

et al. 2016

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Objective A direct renin inhibitor, aliskiren, has a longer stable antihypertensive effect compared with other renin-angiotensin-aldosterone system (RAAS) inhibitors. Methods This study was a 6-month, single-center, open trial conducted between December 2010 and November 2011 to assess the antihypertensive effect of adding aliskiren (300 mg) to the treatment of essential hypertension patients whose target blood pressure (BP) had not been achieved and to assess whether it was possible to reduce the amount of antihypertensive drugs used. Results The results showed an overall improvement in the target BP achievement rate of 60% for clinic BP and 52% for home BP measurements (75 cases total). The mean number of drugs before treatment with aliskiren was 3.28±1.52, whereas at the end of the six months the mean number of drugs prescribed other than aliskiren was 2.85±1.72 (p<0.0001). Moreover, no worsening of the renal function was observed in patients with diabetes or chronic kidney disease (CKD) who were being treated with other RAAS inhibitors in combination to aliskiren. Conclusion These results showed that when aliskiren was added to the treatment of poorly controlled hypertension, the BP achievement rate increased, and it was possible to reduce the amount of antihypertensive drugs used in combination with aliskiren. Moreover, as a result of careful monitoring of the renal function or decreasing the amounts of drugs used in combination, no worsening of the renal function was observed even in the cases complicated by diabetes or CKD being treated with other RAAS inhibitors.

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Pharmacokinetics, Safety, and Tolerability of the Novel Oral Direct Renin Inhibitor Aliskiren in Elderly Healthy Subjects

Cited by 49 publications

References 34 publications

Aliskiren for Geriatric Lowering of Systolic Hypertension: a randomized controlled trial

Aliskiren for Geriatric Lowering of Systolic Hypertension: a randomized controlled trial

Single-Dose Pharmacokinetics of the Renin Inhibitor ACT-077825 in Elderly and Young Subjects of Both Sexes

Antihypertensive Efficacy of the Direct Renin Inhibitor Aliskiren as Add-on Therapy in Patients with Poorly Controlled Hypertension

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