Integrated pharmacokinetics and pharmacodynamics of epoprostenol in healthy subjects

Nicolas, Laurent B.; Krause, Andreas; Gutierrez, Marcelo M.; Dingemanse, Jasper

doi:10.1111/j.1365-2125.2012.04301.x

Cited by 12 publications

(3 citation statements)

References 31 publications

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“…Information regarding the pharmacokinetics/ pharmacodynamics of prostacyclin analogues in patients with advanced CKD is limited and FDA labels do not provide any dosing adjustments [55]. Epoprostenol has a limited half-life of 10 min, and doses are slowly increased over time, making it difficult to study pharmacokinetics because of the rapidity of its clearance [56]. It was previously studied, however, in dialysis patients as an antithrombotic agent at similar doses to the initial dose for pulmonary hypertension [57].…”

Section: Prostacyclin Analogues and Prostacyclin Receptor Antagonistsmentioning

confidence: 99%

Therapeutic approaches for pulmonary hypertension in patients with chronic kidney disease

Tuttle,

Sarnak,

Navaneethan

2024

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of review Pulmonary hypertension is a common comorbidity in patients with chronic kidney disease (CKD), but therapeutic options are limited. We discuss the epidemiology of pulmonary hypertension in patients with CKD and review therapies for pulmonary hypertension with a focus on emerging treatments for pulmonary arterial hypertension (PAH). Recent findings The definition of pulmonary hypertension has been updated to a lower threshold of mean pulmonary artery pressures of more than 20 mmHg, potentially leading to more patients with CKD to qualify for the diagnosis of pulmonary hypertension. Endothelin receptor antagonists, a class of medications, which demonstrated efficacy in patients with PAH, have been shown to slow progression of CKD, but their efficacy in lowering pulmonary artery pressures and their effects on reducing cardiovascular mortality in this population remains unproven. Sotatercept, a novel activin signaling inhibitor, which was previously studied in dialysis patients has been shown to increase exercise capacity in patients with PAH. These studies may lead to new specific therapies for pulmonary hypertension in patients with CKD. Summary Pulmonary hypertension is common in patients with CKD. Although our understanding of factors leading to pulmonary hypertension in this population have evolved, evidence supporting disease-specific therapy in CKD is limited arguing for larger, long-term studies.

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Section: Prostacyclin Analogues and Prostacyclin Receptor Antagonistsmentioning

confidence: 99%

Therapeutic approaches for pulmonary hypertension in patients with chronic kidney disease

Tuttle,

Sarnak,

Navaneethan

2024

Current Opinion in Nephrology &Amp; Hypertension

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“…Studies have demonstrated that the inactive 6-keto-PGF1a hydrolysis product serves as a stable surrogate measure with a linear dose relationship to intravenously infused epoprostenol. 20,21 However, the blood level of 6-keto-PGF1a attributable to hydrolysis of endogenously produced prostacyclin, or exogenously administered epoprostenol, cannot be differentiated. The metabolite, 6-keto PGF1a, was detected at low levels (average <60 pg/mL) immediately post exposure in the blood of control animals as expected, while a dose-related increase was observed in animals inhaling epoprostenol.…”

Section: Summary/conclusionmentioning

confidence: 99%

Novel Toxicology Program to Support the Development of Inhaled VentaProst

Tepper¹,

Pfeiffer²,

Bujold³

et al. 2020

Int J Toxicol

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Currently, off-label continuous administration of inhaled epoprostenol is used to manage hemodynamics during mitral valve surgery. A toxicology program was developed to support the use of inhaled epoprostenol during mechanical ventilation as well as pre- and postsurgery via nasal prongs. To support use in patients using nasal prongs, a Good Laboratory Practice (GLP), 14-day rat, nose-only inhalation study was performed. No adverse findings were observed at ∼50× the dose rate received by patient during off-label use. To simulate up to 48 hours continuous aerosol exposure during mechanical ventilation, a GLP toxicology study was performed using anesthetized, intubated, mechanically ventilated dogs. Dogs inhaled epoprostenol at approximately 6× and 13× the dose rate reported in off-label human studies. This novel animal model required establishment of a dog intensive care unit providing sedation, multisystem support, partial parenteral nutrition, and management of the intubated mechanically ventilated dogs for the 48-hour duration of study. Aerosol was generated by a vibrating mesh nebulizer with novel methods required to determine dose and particle size in-vitro. Continuous pH 10.5 epoprostenol was anticipated to be associated with lung injury; however, no adverse findings were observed. As no toxicity at pH 10.5 was observed with a formulation that required refrigeration, a room temperature stable formulation at pH 12 was evaluated in the same ventilated dog model. Again, there were no adverse findings. In conclusion, current toxicology findings support the evaluation of inhaled epoprostenol at pH 12 in surgical patients with pulmonary hypertension for up to 48 hours continuous exposure.

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“…23 Although clinical studies with the IV administration of epoprostenol AS are limited at present, direct biocompatibility has been shown with respect to pharmacokinetics, pharmacodynamics, safety, and tolerability between epoprostenol GM and epoprostenol AS 24 ; in addition, both products have the same half-life because they contain the same active ingredient. 23 Although clinical studies with the IV administration of epoprostenol AS are limited at present, direct biocompatibility has been shown with respect to pharmacokinetics, pharmacodynamics, safety, and tolerability between epoprostenol GM and epoprostenol AS 24 ; in addition, both products have the same half-life because they contain the same active ingredient.…”

Section: Epoprostenol As (Veletri)mentioning

confidence: 99%

Management of the Patient With Pulmonary Arterial Hypertension Receiving Intravenous Prostacyclin

Kingman

Lombardi

2014

Journal of Infusion Nursing

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Pulmonary arterial hypertension (PAH) is a severely disabling disorder characterized by elevated pulmonary artery pressure ultimately leading to right heart failure and death. Treatment options have significantly increased over the past decade. Intravenous prostacyclins remain the treatment of choice for advanced PAH, leading to long-term clinical benefits and improved survival. Their administration requires a high level of nursing competency and presents considerable challenges for patients and caregivers. This article reviews the characteristics of currently available intravenous prostacyclins and provides a practical guide for nurses who may have had limited exposure to intravenous prostacyclins and their unique dosing, side effects, and titration characteristics.

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Integrated pharmacokinetics and pharmacodynamics of epoprostenol in healthy subjects

Cited by 12 publications

References 31 publications

Therapeutic approaches for pulmonary hypertension in patients with chronic kidney disease

Therapeutic approaches for pulmonary hypertension in patients with chronic kidney disease

Novel Toxicology Program to Support the Development of Inhaled VentaProst

Management of the Patient With Pulmonary Arterial Hypertension Receiving Intravenous Prostacyclin

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