Aliskiren Exhibits Similar Pharmacokinetics in Healthy Volunteers and Patients with Type 2 Diabetes Mellitus

Zhao, Changgeng; Vaidyanathan, Sujata; Yeh, Ching-Ming; Maboudian, Mojdeh; Dieterich, H. A.

doi:10.2165/00003088-200645110-00006

Cited by 62 publications

(54 citation statements)

References 25 publications

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“…After oral administration, peak plasma concentrations (Cmax) of aliskiren are reached within 1-3 hours Zhao et al, 2006). When taken with a high-fat meal, the mean area under the plasma concentration-time curve (AUC) and Cmax of aliskiren are decreased by 71% and 85%, respectively (Novartis_Europharm_Limited 2007.…”

Section: Pharmacokinetic Properties Of Aliskirenmentioning

confidence: 99%

“…Less than 1% of an orally administered dose is excreted in the urine as unchanged drug (Waldmeier et al, 2007). After oral administration of a single 300-mg dose of aliskiren to healthy volunteers, the mean ± SD clearance corrected for bioavailability [i.e., clearance/drug bioavailability (Cl/F)] was 234 ± 137 L/hour (Zhao et al, 2006). The terminal half-life of aliskiren ranges from 24-40 hours (Nussberger et al, 2002;Azizi et al, 2004;Zhao et al, 2006).…”

Section: Pharmacokinetic Properties Of Aliskirenmentioning

confidence: 99%

“…After oral administration of a single 300-mg dose of aliskiren to healthy volunteers, the mean ± SD clearance corrected for bioavailability [i.e., clearance/drug bioavailability (Cl/F)] was 234 ± 137 L/hour (Zhao et al, 2006). The terminal half-life of aliskiren ranges from 24-40 hours (Nussberger et al, 2002;Azizi et al, 2004;Zhao et al, 2006). This half-life, which is longer than the 24-hour dosing interval, is consistent with the observation that plasma concentrations of aliskiren have been shown to accumulate by about 2-fold at steady state compared with administration of a single dose .…”

Section: Pharmacokinetic Properties Of Aliskirenmentioning

confidence: 99%

See 2 more Smart Citations

Efficacy of Aliskiren/Hydrochlorothiazide Combination for the Treatment of Hypertension: A Meta-Analytical Revision

Morgado¹,

Rolo²,

Castelo‐Branco³

2012

Pharmacotherapy

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Section: Pharmacokinetic Properties Of Aliskirenmentioning

confidence: 99%

Section: Pharmacokinetic Properties Of Aliskirenmentioning

confidence: 99%

Section: Pharmacokinetic Properties Of Aliskirenmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy of Aliskiren/Hydrochlorothiazide Combination for the Treatment of Hypertension: A Meta-Analytical Revision

Morgado¹,

Rolo²,

Castelo‐Branco³

2012

Pharmacotherapy

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“…22 The mean terminal half-life is approximately 40 hours after multiple administrations of a single dose, and repeated once-daily administration leads to drug accumulation. 23 The mean absolute bioavailability is 2.6% 24 ; administration with a high-fat meal reduces AUC and C max values by 71% and 85%, respectively, of those in the fasting state, so patients should be advised to take aliskiren in the same manner each day with respect to meal times. 25 Peak plasma concentrations are reached 1 to 2 hours after dosing, 23,24 and steady state is reached after 5 to 8 days of once-daily administration.…”

Section: Aliskiren Pharmacokineticsmentioning

confidence: 99%

“…23 The mean absolute bioavailability is 2.6% 24 ; administration with a high-fat meal reduces AUC and C max values by 71% and 85%, respectively, of those in the fasting state, so patients should be advised to take aliskiren in the same manner each day with respect to meal times. 25 Peak plasma concentrations are reached 1 to 2 hours after dosing, 23,24 and steady state is reached after 5 to 8 days of once-daily administration. 21 The main pathway of elimination for aliskiren is via biliary excretion as unmetabolized drug.…”

Section: Aliskiren Pharmacokineticsmentioning

confidence: 99%

Direct Renin Inhibition: Focus on Aliskiren

Pool¹

2007

JMCP

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BAckgRounD: Despite the availability of many effective, well-tolerated drugs, a significant proportion of treated hypertensive patients still have uncontrolled high blood pressure (BP) and thus face serious morbidity and mortality. The renin-angiotensin aldosterone system (RAAS) is a key target for BP control and for cardiovascular and renal protection. Renin controls the rate-limiting step in the RAAS cascade and hence is the optimal target for RAAS suppression. Aliskiren is the first direct renin inhibitor (DRI) to be approved by the u.S. Food and Drug Administration and the European Medicines Agency for treating hypertension.oBjEcTIvE: To provide an overview of the pharmacology, pharmacokinetics, preclinical, and clinical efficacy and safety data on the DRI aliskiren.RESulTS: Approximately 70% of essential hypertension is associated with elevated renin levels. Aliskiren is a potent and highly specific inhibitor of renin, with oral bioavailability of 2.6% and an elimination half-life of 40 hours, making it suitable for once-daily oral administration. Aliskiren dose-dependently reduced BP, inhibited plasma renin activity (PRA), attenuated renal damage in animal models, and showed efficient and longer-lasting blockade of the RAAS in normotensive human subjects compared with other RAAS inhibitors. The clinical efficacy and safety of aliskiren have been evaluated both as monotherapy and in combination with other antihypertensive agents in phase II and phase III trials of patients with mild to severe hypertension. When used as monotherapy, aliskiren led to significant dose-dependent reductions in BP from baseline that were greater than those obtained with placebo and comparable with those achieved with an angiotensin II receptor blocker (ARB). The combination of aliskiren with a diuretic, a calcium channel blocker (ccB), an angiotensin-converting enzyme inhibitor (AcEI), or an ARB generally had greater and longer-lasting BP-lowering efficacy than did single agents alone. Aliskiren also countered the reactive increase in PRA caused by diuretic, ccB, AcEI, and ARB therapy. once-daily treatment with aliskiren was well tolerated.concluSIonS: As a DRI, aliskiren blocks the RAAS more completely than do other current downstream RAAS inhibitors. When used once daily, aliskiren is a safe and effective antihypertensive agent that can be used as monotherapy or in combination with other agents to provide additional options to improve BP control.

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Antihypertensives: Renin Inhibitors

Tice¹,

McGeehan²,

Claremon³

2010

Burger's Medicinal Chemistry and Drug Discovery

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Renin has been recognized as an attractive target for antihypertensive drugs since the 1950s. Intensive efforts in the 1980s focused on peptidomimetic hydroxy transition‐state isosteres led to many potent renin inhibitors. However, none of these compounds was developed as a drug. The advent of routine X‐ray crystallography of protein–ligand complexes provided additional insights that culminated in the discovery of aliskiren, a fully nonpeptidic renin inhibitor. Aliskiren, the first direct renin inhibitor to reach the market, was approved as an antihypertensive in 2007. Preliminary clinical trials suggest that aliskiren, and potentially other direct renin inhibitors, may have utility in end organ protection and congestive heart failure, in addition to hypertension.

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Aliskiren Exhibits Similar Pharmacokinetics in Healthy Volunteers and Patients with Type 2 Diabetes Mellitus

Cited by 62 publications

References 25 publications

Efficacy of Aliskiren/Hydrochlorothiazide Combination for the Treatment of Hypertension: A Meta-Analytical Revision

Efficacy of Aliskiren/Hydrochlorothiazide Combination for the Treatment of Hypertension: A Meta-Analytical Revision

Direct Renin Inhibition: Focus on Aliskiren

Antihypertensives: Renin Inhibitors

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