alexa Oral direct renin inhibition: premise, promise, and potential limitations of a new antihypertensive drug.


Journal of Drug Metabolism & Toxicology

Author(s): Shafiq MM, Menon DV, Victor RG

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Abstract The first oral direct renin inhibitor, aliskiren, recently received approval for the treatment of hypertension. This article addresses the premise, promise, and potential limitations of this new class of renin-angiotensin system inhibitor. Although aliskiren adds to a list of more than 100 drugs approved for the treatment of hypertension, its introduction into clinical medicine is of particular interest because of the novel mechanism of action: inhibition of renin's catalytic activity, the most proximal and rate-limiting step in renin-angiotensin system activation. By producing more complete renin-angiotensin system inhibition than with existing agents, direct renin inhibitors may afford greater protection from hypertensive complications. Other potential advantages include additional blood pressure reduction when used in combination therapy, a placebo-like side-effect profile, avid renal concentration, and long duration of action. Potential limitations include modest levels of blood pressure reduction that are equivalent to but not greater than angiotensin receptor blockers, reduced gastrointestinal absorption with a high-fat meal, and large reactive increases in renin secretion--the functional importance of which is under intense investigation. The results of outcomes trials are eagerly awaited.
This article was published in Am J Med and referenced in Journal of Drug Metabolism & Toxicology

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