The effects of aldosterone synthase inhibition on aldosterone and cortisol in patients with hypertension: a phase II, randomized, double-blind, placebo-controlled, multicenter study.

2.50
Hdl Handle:
http://hdl.handle.net/2336/295042
Title:
The effects of aldosterone synthase inhibition on aldosterone and cortisol in patients with hypertension: a phase II, randomized, double-blind, placebo-controlled, multicenter study.
Authors:
Andersen, Karl; Hartman, Daniel; Peppard, Thomas; Hermann, David; Van Ess, Peter; Lefkowitz, Martin; Trapani, Angelo
Citation:
J Clin Hypertens (Greenwich) 2012, 14 (9):580-7
Issue Date:
Sep-2012
Abstract:
Blockade of the renin-angiotensin-aldosterone system (RAAS) is an established method to lower blood pressure in patients with hypertension. Aldosterone, the end product of the RAAS cascade, acts by increasing salt reabsorption in the kidney and catecholamine release from the adrenal medulla. Currently available aldosterone inhibitors have the disadvantage of increasing circulating aldosterone and thus may lead to aldosterone breakthrough. Aldosterone synthase inhibition (ASI) is a novel approach to suppressing the RAAS. Due to homology between the enzymes responsible for aldosterone synthesis (CYP11B2) and cortisol synthesis (CYP11B1), the blockade of aldosterone synthesis may also suppress cortisol release. The authors evaluated the effect of the novel ASI LCI699 on the cortisol response to adrenocorticotropic hormone (ACTH) stimulation in patients with hypertension in order to find the maximally tolerated dose (MTD) in this patient population. Among the 63 patients evaluated, there was a dose- and time-dependent effect of LCI699 on both aldosterone and ACTH-stimulated cortisol. Based on exposure-response analysis, the MTD was estimated to be 1.30 mg once daily with a 90% prediction interval of 0.88 mg once daily to 1.81 mg once daily. No patients required intervention for adrenal insufficiency. LCI699 was well tolerated with no serious adverse events.
Additional Links:
http://dx.doi.org/10.1111/j.1751-7176.2012.00667.x
Rights:
Archived with thanks to Journal of clinical hypertension (Greenwich, Conn.)

Full metadata record

DC FieldValue Language
dc.contributor.authorAndersen, Karlen_GB
dc.contributor.authorHartman, Danielen_GB
dc.contributor.authorPeppard, Thomasen_GB
dc.contributor.authorHermann, Daviden_GB
dc.contributor.authorVan Ess, Peteren_GB
dc.contributor.authorLefkowitz, Martinen_GB
dc.contributor.authorTrapani, Angeloen_GB
dc.date.accessioned2013-07-02T09:35:44Z-
dc.date.available2013-07-02T09:35:44Z-
dc.date.issued2012-09-
dc.date.submitted2012-07-02-
dc.identifier.citationJ Clin Hypertens (Greenwich) 2012, 14 (9):580-7en_GB
dc.identifier.issn1751-7176-
dc.identifier.pmid22947355-
dc.identifier.doi10.1111/j.1751-7176.2012.00667.x-
dc.identifier.urihttp://hdl.handle.net/2336/295042-
dc.description.abstractBlockade of the renin-angiotensin-aldosterone system (RAAS) is an established method to lower blood pressure in patients with hypertension. Aldosterone, the end product of the RAAS cascade, acts by increasing salt reabsorption in the kidney and catecholamine release from the adrenal medulla. Currently available aldosterone inhibitors have the disadvantage of increasing circulating aldosterone and thus may lead to aldosterone breakthrough. Aldosterone synthase inhibition (ASI) is a novel approach to suppressing the RAAS. Due to homology between the enzymes responsible for aldosterone synthesis (CYP11B2) and cortisol synthesis (CYP11B1), the blockade of aldosterone synthesis may also suppress cortisol release. The authors evaluated the effect of the novel ASI LCI699 on the cortisol response to adrenocorticotropic hormone (ACTH) stimulation in patients with hypertension in order to find the maximally tolerated dose (MTD) in this patient population. Among the 63 patients evaluated, there was a dose- and time-dependent effect of LCI699 on both aldosterone and ACTH-stimulated cortisol. Based on exposure-response analysis, the MTD was estimated to be 1.30 mg once daily with a 90% prediction interval of 0.88 mg once daily to 1.81 mg once daily. No patients required intervention for adrenal insufficiency. LCI699 was well tolerated with no serious adverse events.en_GB
dc.description.sponsorshipNovartisen_GB
dc.language.isoenen
dc.relation.urlhttp://dx.doi.org/10.1111/j.1751-7176.2012.00667.xen_GB
dc.rightsArchived with thanks to Journal of clinical hypertension (Greenwich, Conn.)en_GB
dc.subject.meshAdolescenten_GB
dc.subject.meshAdulten_GB
dc.subject.meshAgeden_GB
dc.subject.meshAldosteroneen_GB
dc.subject.meshAldosterone Synthaseen_GB
dc.subject.meshArterial Pressureen_GB
dc.subject.meshDouble-Blind Methoden_GB
dc.subject.meshFemaleen_GB
dc.subject.meshHumansen_GB
dc.subject.meshHydrocortisoneen_GB
dc.subject.meshHypertensionen_GB
dc.subject.meshImidazolesen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshProspective Studiesen_GB
dc.subject.meshPyridinesen_GB
dc.subject.meshRenin-Angiotensin Systemen_GB
dc.subject.meshYoung Adulten_GB
dc.titleThe effects of aldosterone synthase inhibition on aldosterone and cortisol in patients with hypertension: a phase II, randomized, double-blind, placebo-controlled, multicenter study.en
dc.typeArticleen
dc.contributor.departmentEncode Clinic, Reykjavik, Iceland. andersen@landspitali.isen_GB
dc.identifier.journalJournal of clinical hypertension (Greenwich, Conn.)en_GB
dc.rights.accessLandspitali Access - LSH-aðganguren

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