Long‐term study of oral treprostinil to treat pulmonary arterial hypertension: dosing, tolerability, and pharmacokinetics

White, R. James; Parikh, Keyur; Allen, Roblee P.; Feldman, Jeremy; Jerjez-Sanchez, Carlos; Pan, Lei; Keogh, Anne; Vizza, Carmine Dario; Shapiro, Shelley; Gordon, Kathryn; Broderick, Meredith; Bartolome, Sonja

doi:10.1177/2045894019866335

Cited by 4 publications

(4 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…46 Treprostinil 2 administered to PAH patients orally or by infusion does not have a dose cap and is titrated to effect and clinical tolerability. 47 As with other prostacyclin drugs used to treat PAH, at higher concentrations, dose is limited by systemic toxicity. Additionally, the utility of subcutaneously infused treprostinil is restrained by local side effects.…”

Section: Resultsmentioning

confidence: 99%

Synthetic routes to treprostinil N-acyl methylsulfonamide

Picken

Laing

Shen

et al. 2020

Tetrahedron Letters

View full text Add to dashboard Cite

The synthesis of the prodrug candidate, treprostinil N-acyl methylsulfonamide 5 was accomplished from treprostinil 2 utilising protecting group strategies. A more direct synthesis for the prodrug was also achieved using a treprostinil triol precursor 12 and bromoacetyl acylmethylsulfonamide 14. The overall yield of treprostinil N-acyl sulfonamide 5 directly from the triol precursor 12 is similar to the protecting group strategies because deprotonation of the acidic proton in the bromoacetyl acylmethylsulfonamide 14 reduces electrophilicity. However, the more direct route using the treprostinil triol precursor holds greater promise as a strategy to prepare a wide range of treprostinil prodrug candidates. Treprostinil N-acyl methylsulfonamide prodrug 5 exhibited a 30-fold decrease in the potency at the human prostacyclin (IP) receptor compared to treprostinil 2 in an in vitro cyclic AMP assay.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthetic routes to treprostinil N-acyl methylsulfonamide

Picken

Laing

Shen

et al. 2020

Tetrahedron Letters

View full text Add to dashboard Cite

show abstract

“…This was perhaps most evident in those patients who were previously receiving twice daily dosing of oral treprostinil in the study by Chakinala et al, wherein the dosing was changed to three times daily as part of an amended protocol to mitigate peak and trough drug differences with improved tolerability [ 7 ]. Another study by White et al further demonstrated that a three times daily regimen for oral treprostinil provides reduced peak-to-trough ratios, which in turn improves tolerability to achieve goal doses [ 8 ]. Nonetheless, predicting a patient’s tolerability of oral treprostinil, in comparison to IV formulations, remains difficult, with speculation of a pharmacokinetic relationship to adverse effect incidence.…”

Section: Discussionmentioning

confidence: 99%

Escalating Oral Treprostinil Dose With Intravenous Treprostinil Bridging Therapy

Perez,

Williams,

Rahaghi

2024

Cureus

View full text Add to dashboard Cite

Oral treprostinil, approved for the treatment of pulmonary arterial hypertension, remains an attractive option in combination with other medications to delay disease progression and improve exercise capacity. However, patients are often challenged with the ability to overcome adverse effects as outpatients and reach effective doses in a timely manner. We describe a case of a 47-year-old female on oral treprostinil who presented to the clinic with worsening symptoms of disease, necessitating higher dosing. This patient was previously uptitrated outpatient with oral treprostinil, which had allowed her to remain stable for years. Once uptitrated with additional intravenous therapy, the oral treprostinil dose was gradually further increased to the new goal dosage, resulting in improvements in symptoms and right ventricular function. This case highlights the versatility of dose optimization of oral treprostinil with rapid bridging through intravenous therapy.

show abstract

“…55,56 The experts recommend the use of treprostinil based on the fact that it shows improved PVR and exercise capacity and decreases the risk profile. [55][56][57][58][59][60] It is important to discuss that the recommendation for females does not exclude males. Treprostinil, like all therapies, can be used in either gender; however, the recommendation is based on a clinical trial with a female predominance.…”

Section: Median: 85 (Iqr 1)mentioning

confidence: 99%

Expert consensus on the stratification, management, and follow-up of patients with Group 1 pulmonary hypertension at intermediate risk

Conde-Camacho¹,

Orozco-Levi²,

Londoño³

et al. 2023

RCCARE

View full text Add to dashboard Cite

Introduction: stratification of risk for major complications (including mortality) is the current fundamental clinical strategy for making therapeutic decisions in patients with pulmonary arterial hypertension. However, it is noticeable that most patients are grouped in the intermediate category both at the time of diagnosis and during follow-up, highlighting the relevance and necessity of improving discrimination and therapeutic options for patients at intermediate risk. Objective: to define a series of recommendations on the proper subclassification, follow-up, and treatment of adult patients with pulmonary arterial hypertension at intermediate risk, adapted to the Colombian context. Method: fifteen experts in pulmonary hypertension were invited to participate. They voted on 14 questions, using the modified Delphi methodology, and a systematic review of the literature on these questions was carried out in several bibliographic bases: VHL, Cochrane Library, PubMed, Medline and Web of Science. The MeSh and DeCs criteria for each question were used without language or time limits. Results and discussion: the present study provides a series of 18 consensus recommendations on stratification, treatment and other sections. Additionally, the initiative shows the paucity of scientific studies in our country to identify the behavior of this disease along with the barriers to access and availability of medicines in our country.

show abstract

Long‐term study of oral treprostinil to treat pulmonary arterial hypertension: dosing, tolerability, and pharmacokinetics

Cited by 4 publications

References 23 publications

Synthetic routes to treprostinil N-acyl methylsulfonamide

Synthetic routes to treprostinil N-acyl methylsulfonamide

Escalating Oral Treprostinil Dose With Intravenous Treprostinil Bridging Therapy

Expert consensus on the stratification, management, and follow-up of patients with Group 1 pulmonary hypertension at intermediate risk

Contact Info

Product

Resources

About