Aliskiren ( Rasilez ) is the first in a new class of orally-administered rennin inhibitors, and is under investigation for the treatment of hypertension.

Renin is an enzyme released by specialized cells of the kidney into the blood. It is in response to sodium depletion or low blood volume. Renin converts angiotensinogen ( a protein released into the blood by the liver ) to angiotensin I.
Angiotensin I is converted to angiotensin II by an enzyme in the veins of the lungs.
Angiotensin II acts on the adrenal cortex to stimulate the release of aldosterone. Aldosterone acts on the distal tubules of the kidneys to decrease the loss of sodium ions and secondarily fluid.
This has the effect of increasing blood pressure.
In addition, angiotensin causes constriction of small blood vessels, which also increases blood pressure.

In a randomized, double-blind, multi-center, placebo-controlled study led by the Seoul National University College of Medicine in South Korea, 672 patients were randomized to 150, 300 or 600 mg of Aliskiren or placebo, once daily for eight weeks.

All patients had mild to moderate hypertension [ resting diastolic blood pressure ( DBP ) of 95 to less than 110 mmHg ].

Aliskiren significantly lowered the DBP and resting systolic blood pressure ( SBP ) dose-dependently overall, in all patients, compared to placebo.

The proportion of treatment responders ( those who experienced a greater than 10 mmHg reduction in DBP and/or DBP less than 90 mmHg at endpoint ) was significantly higher in patients receiving Aliskiren – 150 mg ( 59% ), 300 mg ( 63% ) or 600 mg ( 69% ) – versus placebo ( 36% ).

The drug remained effective over the 24-hour dosing period, and demonstrated the same side effects as placebo up to the 300 mg dose.
At the 600 mg dose, patients experienced a greater incidence of diarrhea, but there were no serious side effects in any of the dosage groups or the placebo group.

" Aliskiren is an effective antihypertensive drug for patients with mild-to-moderate hypertension, without serious side effects, " said Byung-Hee Oh, of Seoul National University College of Medicine and lead author of the study.

Source: American College of Cardiology – Meeting, 2006


XagenaMedicine2006