Ambrisentan for the Treatment of Pulmonary Arterial Hypertension

Abstract

Objective:

To review the pharmacology, pharmacokinetics, efficacy, and safety of ambrisentan, a selective endothelin type A (ET_A) receptor antagonist, for the treatment of pulmonary arterial hypertension (PAH).

Data Sources:

Articles were identified through a search of the MEDLINE (1950–November 2007) database for English-language articles containing the key words ambrisentan, pulmonary arterial hypertension, pulmonary hypertension, endothelin antagonist, and endothelin type A receptor. References from publications identified in this search were reviewed for relevant information. Unpublished data received from the manufacturer were also included in this review.

Study Selection and Data Extraction:

All articles identified from the data search were reviewed for relevant information. Applicable information was included in this review.

Data Synthesis:

Ambrisentan is the first oral nonsulfonamide ET_A receptor antagonist approved by the FDA for use in patients with PAH who have World Health Organization class II or III symptoms. To date, the use of ambrisentan in the treatment of PAH has been evaluated by only 1 published Phase 2 clinical trial and 3 unpublished Phase 3 clinical trials. Ambrisentan therapy during clinical trials resulted in a significant improvement in exercise capacity and hemodynamic parameters. Metabolism occurs by hepatic glucuronidation, with elimination primarily through nonrenal pathways. A half-life of 15 hours allows for once-daily dosing. The most common adverse effect reported during clinical trials was peripheral edema. Hepatotoxicity occurred very infrequently, with affected patients requiring only a dose reduction to resolve an episode of elevated aminotransferases.

Conclusions:

Ambrisentan appears to be a promising treatment option for patients affected by PAH, given its improved drug–drug interaction and hepatotoxicity profile compared with other endothelin antagonists. Future studies are needed to determine the role of ambrisentan in the treatment of PAH and the selection of optimal endothelin antagonism.

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