Table 2.

Comparison of pharmacokinetics, side effects, contraindications of the most commonly used drugs which target the prostacyclin pathway.

Drug1	Route of administration	Pharmacokinetics	Side effects related to the route of administration	Side effects not related to the route of administration
Epoprostenol [50, 51]	i.v. infusion (Flolan®, Veletri®)	Bioavailability: 100% Metabolism: Spontaneous degradation in blood Enzymatic degradation in the liver Elimination: Mainly urine (84%) T½ < 6 min	Bleeding Infection (catheter-related) Malfunction of the infusion pump Pain Sepsis Thromboembolic event	Anorexia Diarrhoea Dizziness Flushing Headache Hypotension Jaw pain Musculoskeletal pain Nausea Vomiting Tachycardia Vasodilatation
Treprostinil [52, 53, 54]	s.c. infusion2 (Remodulin®, Tresuvi®, Trepulmix®)	Bioavailability: 100% Metabolism: Degradation in the liver (primarily CYP2C8) Elimination: Mainly urine (79%) T½ 2–4 h	Abscess Bleeding/bruising Infection (infusion pump-related) Malfunction of the infusion pump Pain Other site reactions (erythema, induration, rash)	Bleeding Diarrhoea Dizziness Headache Hypotension Jaw pain Nausea Edema Vomiting Tachycardia Vasodilatation
	i.v. infusion3 (Remodulin® Tresuvi®)	Bioavailability: 100% Metabolism: Degradation in the liver (primarily CYP2C8) Elimination: Mainly urine (79%) T½ 2–4 h	Abscess Bleeding/bruising Infection (catheter-related) Malfunction of the infusion pump Pain Sepsis Thrombophlebitis Other site reactions (swelling, paraesthesia’s, erythema, induration, rash)
	Inhalation (Tyvaso®)	Bioavailability: 64–72% Metabolism: Degradation in the liver (primarily CYP2C8) Elimination: Mainly urine (70%) T½ 3–4 h	Cough Epistaxis Hemoptysis Nasal discomfort throat irritation Throat pain Wheezing	Diarrhoea Dizziness Flushing Headache Nausea Tachycardia Vasodilatation
	p.o. (Orenitram®)	Bioavailability: 17% Metabolism: Degradation in the liver (primarily CYP2C8) Elimination: Mainly urine (70%) T½ 1–1.5 h	Abdominal discomfort Diarrhoea Nausea Vomiting	Flushing Headache Jaw pain Hypokalemia
Iloprost [55]	Inhalation (Ventavis®)	Bioavailability: 63% Metabolism: Oxidation in the liver Elimination: Mainly urine (68%) T½ 20–30 min	Cough Epistaxis Hemoptysis Nasal discomfort throat irritation Throat pain	Diarrhoea Dizziness Flushing Headache Hypotension Insomnia Jaw pain Nausea Vomiting Tachycardia Vasodilatation
Beraprost [56]	p.o. (Beraprost®)	Bioavailability: 50–70% Metabolism: Degradation in the liver Elimination: Mainly faeces (75%) T½ 30–40 min	Diarrhoea Nausea	Flushing Headache Increased bilirubin, lactate dehydrogenase, triglycerides
Selexipag [34, 57]	p.o. (Uptravi®)	Bioavailability: 49% Metabolism: Hydrolysis in the liver and intestine (primarily CYP2C8) Elimination: Mainly feaces (93%) T½ 3–4 h	Diarrhoea Decreased appetite Nausea Vomiting	Anaemia Arthralgia Headache Hyperthyroidism Flushing Myalgia Rash

¹Contraindications to the use of any of the PGI₂ analogues: heart failure with reduced left ventricular ejection fraction, severe hepatic impairment (Child Pugh class C), concomitant use of strong inhibitors of CYP2C8 (e.g. gemfibrozil), hypersensitivity to the drug;

²The preferred administration route of treprostinil;

³External or implantable intravenous infusion pump