Differential response to intravenous prostacyclin analog therapy in patients with pulmonary arterial hypertension

Walkey, Allan J.; Fein, Daniel G.; Horbowicz, Kevin; Farber, Harrison W.

doi:10.1016/j.pupt.2011.01.002

Cited by 8 publications

(5 citation statements)

References 13 publications

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“…The discrepancy between plasma drug concentrations and duration of hemodynamic benefit may be explained by storage in lung tissue following inhalation, or this may reflect the duration of receptor binding and signaling at the cellular level. The duration of hemodynamic response following acute intravenous administration has not been described, although discontinuation of chronic intravenous treprostinil in five PAH patients led to a significant increase in pulmonary artery pressure within 1 h [59].…”

Section: Pharmacokinetics and Metabolismmentioning

confidence: 98%

Inhaled treprostinil for the treatment of pulmonary arterial hypertension

LeVarge

Channick

2012

Expert Review of Respiratory Medicine

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Treprostinil is a prostacyclin derivative approved for the treatment of pulmonary arterial hypertension by intravenous, subcutaneous and inhalational administration. Unlike its precursor epoprostenol, treprostinil is chemically stable at room temperature and neutral pH, and its plasma half-life is longer. In addition to promoting smooth muscle relaxation in the pulmonary vasculature, treprostinil has suppressive effects on platelet aggregation, smooth muscle proliferation and inflammation. A Phase III study, investigating the addition of inhaled treprostinil to oral bosentan or sildenafil, confirmed significant improvements in exercise capacity and quality of life. This review examines the pharmacodynamics, pharmacokinetics, clinical efficacy and safety of inhaled treprostinil for use in pulmonary arterial hypertension.

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Section: Pharmacokinetics and Metabolismmentioning

confidence: 98%

Inhaled treprostinil for the treatment of pulmonary arterial hypertension

LeVarge

Channick

2012

Expert Review of Respiratory Medicine

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“…3 There are no trials directly comparing the therapeutic equivalency of epoprostenol to IV treprostinil, although a small case series reported an inadequate clinical response in 5 patients with severe, decompensated PAH despite high-dose IV treprostinil. 29 These patients were transitioned to epoprostenol and all manifested a robust hemodynamic and functional response. 29 This suggests that there may be differential responses among some individuals to IV prostanoids, possibly secondary to variability of receptor targeting between the drugs.…”

Section: Equivalency Of Drugsmentioning

confidence: 99%

“…29 These patients were transitioned to epoprostenol and all manifested a robust hemodynamic and functional response. 29 This suggests that there may be differential responses among some individuals to IV prostanoids, possibly secondary to variability of receptor targeting between the drugs. 29 Among the other classes, there are observational, retrospective data in ERAs suggesting differential responses to therapy between different races and sexes.…”

Section: Equivalency Of Drugsmentioning

confidence: 99%

“…29 This suggests that there may be differential responses among some individuals to IV prostanoids, possibly secondary to variability of receptor targeting between the drugs. 29 Among the other classes, there are observational, retrospective data in ERAs suggesting differential responses to therapy between different races and sexes. 30 Further study would be needed to confirm these findings.…”

Section: Equivalency Of Drugsmentioning

confidence: 99%

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Gaps and Controversies of New Treatment Recommendations in Recent Pulmonary Hypertension Guidelines: What We Know and What We Don't

Ruopp

Farber

2017

Advances in Pulmonary Hypertension

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Pulmonary arterial hypertension (PAH) is a rare, severe disease of the small pulmonary arteries that is characterized by increased pulmonary vascular resistance and ultimately progression to right heart failure.1 Broadly categorized as World Health Organization (WHO) Group 1 PAH, it encompasses a heterogeneous group of underlying disorders.2–4 Despite the development of new treatment options and strategies over the past 2 decades, survival rates in newly diagnosed patients at 5 years are only 61.2%, and are even poorer in patients with advanced disease.5 New European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension guidelines were released in 2015, with redesigned treatment algorithms aimed at addressing the recent advances in PAH medications, treatment initiation strategies, and treatment goals.3 Though much progress has been made, many areas of uncertainty remain, and some aspects of the 2015 ESC/ERS recommendations are still controversial. Herein, we will discuss some of the gaps and controversies within the recommendations for treatment-naïve WHO Group 1 PAH patients.

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“…The same treprostinil vials are used for subcutaneous and intravenous administration; differences in costs between patients with the two formulations do not reflect cost of the drug per se but are generally due to variances in dosing related to tolerability and increased expense associated with intravenous catheter maintenance. Although nearly all patients transitioned from intravenous epoprostenol to intravenous treprostinil remain stable, there are rare patients who deteriorate after transition (observational cases); furthermore, there are rare patients who are receiving intravenous treprostinil without prior intravenous epoprostenol who do not adequately improve when receiving intravenous treprostinil but do improve with transition from the intravenous treprostinil to intravenous epoprostenol (Walkey et al, 2011).…”

Section: Clinical Studies (Inhalation)mentioning

confidence: 99%