Treprostinil

Treprostinil is a stable tricyclic analog of prostacyclin3 that promotes vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation (Feldman J et al 2020). It relieves symptoms in patients with pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (Feldman J et al 2020).

Treprostinil is a stable analog of prostacyclin, a prostaglandin that acts as an antithrombotic agent and potent vasodilator. Prostacyclin analogs are useful in the treatment of pulmonary arterial hypertension (PAH), a disease characterized by abnormally high blood pressure in the arteries between the heart and lungs (Ding M et al 2021). PAH leads to right heart failure due to remodeling of the pulmonary arteries, and patients with this disease have a poor prognosis (Feldman J et al 2020).

Treprostinil binds and activates the prostacyclin receptor, prostaglandin D2 receptor 1, and prostaglandin E2 receptor 2.3 Activation of these receptors leads to an increase in intracellular cyclic adenosine monophosphate (cAMP), which subsequently promotes the opening of calcium-activated potassium channels leading to cell hyperpolarization (Ding M et al. 2021).3 This mechanism promotes direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation (Del Pozo R etal. 2017). In addition to its direct vasodilatory effect, treprostinil also inhibits inflammatory processes (Ding M et al. 2021).

As an analog of prostacyclin, treprostinil promotes vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation.

Through the FDA, treprostinil has been approved for the treatment of pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease to improve exercise capacity. It is also used to treat pulmonary arterial hypertension in patients who need to be switched from epoprostenol.

Because of its ability to inhibit platelet aggregation, treprostinil may increase the risk of bleeding, and patients with low systemic arterial pressure taking treprostinil may experience symptomatic hypotension. Abrupt discontinuation of treprostinil or drastic dose changes may exacerbate symptoms of pulmonary arterial hypertension (PAH). Inhalation of treprostinil may also cause bronchospasm in patients with asthma, chronic obstructive pulmonary disease (COPD), or bronchial hyperresponsiveness.5 When administered intravenously, treprostinil may cause infusion complications and increase the risk of bloodstream infections.

Treprostinil was approved by the FDA in 2002 for the treatment of pulmonary arterial hypertension. It is available in the following dosage forms: subcutaneous, intravenous, inhaled, and oral. The first generic form of treprostinil became available in 2019 (Feldman J et al 2020).

1. Del Pozo R etal. (2017) The prostacyclin pathway in pulmonary arterial hypertension: a clinical review. Expert Rev Respir Med 11:491-503.
2. Ding M et al (2021) Treprostinil, a prostacyclin analog, ameliorates renal ischemia-reperfusion injury: preclinical studies in a rat model of acute kidney injury. Nephrol Dial Transplant 36:257-266.
3. Lindegaard Pedersen M et al (2019) The prostacyclin analogue treprostinil in the treatment of pulmonary arterial hypertension. Basic Clin Pharmacol Toxicol. 2019 Aug 12. doi: 10.1111/bcpt.13305. [Article.]
4. Feldman J et al (2020) Treprostinil in the treatment of pulmonary arterial hypertension. Future Cardiol 16:547-558.