Antihypertensive — aliskiren fumarate

Hypertension, the elevation of arterial blood pressure, is a common condition with a range of possible causes. One of the most common treatments is the use of angiotensin converting enzyme, or ACE, inhibitors. However, this class of drugs has common side-effects, including angioneurotic oedema.

A different strategy is to interfere with the first, and rate-limiting, step in the cascade — the conversion of renin to angiotensin I by the enzyme angiotensinogen. Renin is the only known substrate for this enzyme, and so a renin inhibitor could prove a very useful and selective drug for treating hypertension. The compound aliskiren,¹ formerly known as CGP-60536, was found to be a highly potent inhibitor of human renin in vitro, and was developed by Novartis.

In a randomised, placebo controlled, parallel group crossover trial, 18 healthy male volunteers were given the drug in escalating doses, or the ACE inhibitor enalapril, or placebo, over a period of 8 days.² Aliskiren inhibited all components of the renin–angiotensin cascade, giving dose-dependent decreases in plasma renin activity, and also lowered the levels of both angiotensin I and II. It remained effective for up to 24hrs, and a dose of 160mg proved equivalent to 20mg enalapril. It was well tolerated, and the only side-effect seen was headache.

In another trial in 226 patients were given single daily oral doses of aliskiren ranging from 37.5mg to 300mg, or 100mg of the angiotensin II blocker losartan, over a period of four weeks.³ No major differences in safety were seen between the two drugs, and a clear dose–response curve of reducing blood pressure was seen. Aliskiren is currently undergoing Phase II trials for the treatment of hypertension, as well as heart failure and chronic kidney failure.