Drug & Device Development

Ambrisentan promising in portopulmonary hypertension

Last Updated: 2011-01-26 17:35:24 -0400 (Reuters Health)

By David Douglas

NEW YORK (Reuters Health) - In patients with portopulmonary hypertension (POPH), ambrisentan can significantly improve pulmonary hemodynamic responses without impairing hepatic function, researchers report in the January issue of Chest.

"The role of ambrisentan in POPH merits further study given the adequate response and tolerability observed in this small cohort of patients," said Dr. Rodrigo Cartin-Ceba in email to Reuters Health.

Dr. Cartin-Ceba and colleagues at the Mayo Clinic, Rochester, Minnesota note that ambrisentan, a selective endothelin-receptor antagonist, is approved by the US Food and Drug Administration for the treatment of pulmonary arterial hypertension.

POPH is an uncommon complication of portal hypertension, seen particularly in patients with cirrhosis.

IV epoprostenol is currently the best-studied drug for the treatment of POPH, but it requires a continuous delivery system. The oral agents sildenafil and bosentan also have disadvantages.

To investigate the effect of ambrisentan oral monotherapy, the team observed 13 patients with POPH for a median of about 20 months. They received no more than 10 mg of the agent daily for a median of around 13 months.

Mean pulmonary artery pressure decreased significantly from a baseline median of 58 mm Hg to 41 mm Hg. The median pulmonary vascular resistance fell from 445 to 174 dynes/s/cm 5.

Liver function tests showed no difference between baseline and 12 months. There was also no effect on renal function or deterioration in systemic blood pressure.

Two patients died, one of advanced hepatocellular carcinoma and one of septic shock following pneumonia. One patient underwent successful liver transplantation and had normalized pulmonary hemodynamic responses afterward.

Overall, the researchers conclude that "that monotherapy with ambrisentan is effective and safe for the treatment of patients with POPH."

SOURCE: http://bit.ly/h1hj6w

Chest 2011;139:109-114.