Abstract:
:Riociguat is approved for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Some patients have difficulty swallowing tablets; therefore, 2 randomized, nonblinded, crossover studies compared the relative bioavailability of riociguat oral suspensions and immediate-release (IR) tablet and of crushed-tablet preparations versus whole IR tablet. In study 1, 30 healthy subjects received 5 single riociguat doses: 0.3 and 2.4 mg (0.15 mg/mL suspensions), 0.15 mg (0.03 mg/mL), and 1.0 mg (whole IR tablet) under fasted conditions and 2.4 mg (0.15 mg/mL) after a high-fat, high-calorie American-style breakfast. In study 2, 25 healthy men received 4 single 2.5-mg doses: whole IR tablet and crushed IR tablet suspended in applesauce and water, respectively, under fasted conditions, and whole IR tablet after a continental breakfast. In study 1, dose-normalized pharmacokinetics of riociguat oral suspensions and 1.0-mg whole IR tablet were similar in fasted conditions; 90% confidence intervals for riociguat area under the curve (AUC) to dose and mean maximum concentration (C max) to dose were within bioequivalence criteria. After food, dose-normalized AUC and C max decreased by 15% and 38%, respectively. In study 2, riociguat exposure was similar for all preparations; AUC ratios for crushed-IR-tablet preparations to whole IR tablet were within bioequivalence criteria. The C max increased by 17% for crushed IR tablet in water versus whole IR tablet. Food intake decreased C max of the whole tablet by 16%, with unaltered AUC versus fasted conditions. Riociguat bioavailability was similar between the oral suspensions and the whole IR tablet; exposure was similar between whole IR tablet and crushed-IR-tablet preparations. Minor food effects were observed. Results suggest that riociguat formulations are interchangeable.
journal_name
Pulm Circjournal_title
Pulmonary circulationauthors
Saleh S,Frey R,Becker C,Unger S,Wensing G,Mück Wdoi
10.1086/685020subject
Has Abstractpub_date
2016-03-01 00:00:00pages
S66-74issue
Suppl 1eissn
2045-8932issn
2045-8940pii
PC2013284journal_volume
6pub_type
杂志文章abstract::The aim of this study was to investigate whether a dual endothelin receptor antagonist bosentan modulates the kinetics of bone marrow-derived stem cells in inhibiting the development of pulmonary hypertension. Bone marrow chimeric mice, transplanted with enhanced green fluorescent protein (eGFP)-positive bone marrow m...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894020919355
更新日期:2020-05-14 00:00:00
abstract::Andeans and Tibetans have less altitude reduction in birth weight than do shorter-resident groups, but only Tibetans are protected from pulmonary hypertension and chronic mountain sickness (CMS). We hypothesized that differences in neonatal oxygenation were involved, with arterial O2 saturation (SaO2) being highest in...
journal_title:Pulmonary circulation
pub_type: 杂志文章,评审
doi:10.1086/679719
更新日期:2015-03-01 00:00:00
abstract::There are limited data on the management of pulmonary arterial hypertension (PAH) in the elderly; therefore, this analysis compared the safety and efficacy of tadalafil between patients ≥65 and <65 years old. This was a post hoc analysis of the randomized, double-blind, placebo-controlled phase 3 Pulmonary Arterial Hy...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/674901
更新日期:2014-03-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is characterized by obstruction of pre-capillary pulmonary arteries, which leads to sustained elevation of pulmonary arterial pressure. Identifying those at risk through early interventions, such as genetic testing, may mitigate disease course. Current practice guidelines recommen...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045893217700156
更新日期:2017-04-01 00:00:00
abstract::Scleroderma-associated pulmonary arterial hypertension (SSc-PAH) is associated with worse outcome than idiopathic pulmonary arterial hypertension (IPAH), potentially due to worse right ventricular adaptation to load as suggested by pressure-volume loop analysis. The value of non-invasive load-adaptability metrics has ...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018788268
更新日期:2018-07-01 00:00:00
abstract::The development of pulmonary arterial hypertension (PAH) in pediatric patients has been linked to the production of the arachidonic acid metabolite, thromboxane A(2) (TxA(2)). The present study evaluated the therapeutic effect of furegrelate sodium, a thromboxane synthase inhibitor, on the development of PAH in a neon...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.4103/2045-8932.97605
更新日期:2012-04-01 00:00:00
abstract::Pregnancy is not advised for patients with Pulmonary hypertension (PH) because of high risk of PH crisis. However, some patients have undiagnosed idiopathic pulmonary arterial hypertension (IPAH) before pregnancy. Upfront combination therapy has high efficacy for patients with IPAH. However, some patients are unable t...
journal_title:Pulmonary circulation
pub_type:
doi:10.1177/2045894020910140
更新日期:2020-02-28 00:00:00
abstract::Hypereosinophilic syndrome is a myeloproliferative disorder characterized by persistent eosinophilia with involvement of multiple organs. The occurrence of severe pulmonary hypertension (PH) in the setting of hypereosinophilic syndrome is very uncommon. A 43-year-old man with documented idiopathic hypereosinophlic syn...
journal_title:Pulmonary circulation
pub_type:
doi:10.1177/2045894018793999
更新日期:2019-01-01 00:00:00
abstract::The biological mechanisms behind the development of pulmonary hypertension in the setting of left heart failure (HF-PH), including combined pre- and post-capillary pulmonary hypertension (Cpc-PH), remains unclear. This study aimed to use candidate polymorphisms in nitric oxide synthase (NOS) genes to explore the role ...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018773049
更新日期:2018-04-01 00:00:00
abstract::Inhaled iloprost is an effective therapy for patients with pulmonary arterial hypertension (PAH); however, some patients experience extended inhalation times when using the V10 formulation (10.0 µg/mL) to deliver a 5 -µg dose (at mouthpiece) and are at risk of incomplete inhalations and reduced inhalation frequency. V...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018798921
更新日期:2018-10-01 00:00:00
abstract::Pulmonary hypertension (PH) comprises a group of pathophysiological syndromes characterized by elevated pulmonary artery pressure and pulmonary vascular resistance, which lead to right ventricular overload, and even right heart failure. PH has a poor prognosis and severely leads to a decline in quality of life. Histor...
journal_title:Pulmonary circulation
pub_type: 杂志文章,评审
doi:10.1177/2045894020937129
更新日期:2020-07-07 00:00:00
abstract::Pulmonary arterial hypertension (PAH) patients have distinct disease courses and responses to treatment, but current diagnostic and treatment schemes provide limited insight. We aimed to see if cluster analysis could distinguish clinical phenotypes in PAH. An unbiased cluster analysis was performed on 17 baseline clin...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045893217705891
更新日期:2017-04-01 00:00:00
abstract::Right ventricular (RV) dysfunction in acute respiratory distress syndrome (ARDS) contributes to increased mortality. Our aim is to identify reproducible transthoracic echocardiography (TTE) parameters of RV dysfunction that can be used to predict outcomes in ARDS. We performed a retrospective single-center cohort pilo...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/685549
更新日期:2016-06-01 00:00:00
abstract::In pulmonary hypertension, as in many other diseases, there is a need for a smarter approach to evaluating new treatments. The traditional randomized controlled trial has served medical science well, but constrains the development of treatments for rare diseases. A workshop was established to consider alternative clin...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.4103/2045-8932.109933
更新日期:2013-01-01 00:00:00
abstract::Rapid access to lung-derived cells from stable subjects is a major challenge in the pulmonary hypertension field, given the relative contraindication of lung biopsy. In these studies, we sought to demonstrate the importance of evaluating a cell type that actively participates in disease processes, as well as the poten...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/688314
更新日期:2016-12-01 00:00:00
abstract::Insulin resistance is highly prevalent in pulmonary arterial hypertension (PAH) patients. However, the long-term impact of diabetes mellitus (DM) on survival in PAH is unclear. Insulin resistance and DM are associated with left ventricular steatosis and dysfunction, but whether the right ventricle (RV) might be affect...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/675994
更新日期:2014-06-01 00:00:00
abstract::Right-ventricular function is a good indicator of pulmonary arterial hypertension (PAH) prognosis; however, how the right ventricle (RV) adapts to the pressure overload is not well understood. Here, we aimed at characterizing the time course of RV early remodeling and discriminate the contribution of ventricular geome...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018800439
更新日期:2018-10-01 00:00:00
abstract::Radiotherapy as a primary treatment for thoracic malignancies induces deleterious effects, such as acute or subacute radiation-induced lung injury (RILI). Although the molecular etiology of RILI is controversial and likely multifactorial, a potentially important cellular target is the lung endothelial cytoskeleton tha...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/686491
更新日期:2016-06-01 00:00:00
abstract::Atrial arrhythmias are common during episodes of acute respiratory failure in patients with chronic lung disease-associated pulmonary hypertension. Expert opinion suggests that management of atrial arrhythmias in patients with pulmonary hypertension should aim to restore sinus rhythm. This is clinically challenging in...
journal_title:Pulmonary circulation
pub_type: 杂志文章,评审
doi:10.1177/2045894020910685
更新日期:2020-03-09 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is a major complication of sickle cell disease (SCD). Low levels of apolipoprotein A1 (Apo-A1) have been implicated in the development of PAH in SCD. We speculate that lower levels of Apo-A1 are related to dysregulation of the ubiquitin-proteasome pathway (UPP). Of 36 recruited pa...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/674763
更新日期:2013-12-01 00:00:00
abstract::Abstract Changes in voltage-gated K(+) (Kv) channel function contribute to the pathogenesis of pulmonary hypertension. Yet the mechanisms underlying Kv channel impairments in the pulmonary circulation remain unclear. We tested the hypothesis that reactive oxygen species (ROSs) contribute to the Kv channel dysfunction ...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/674307
更新日期:2013-09-01 00:00:00
abstract::Inappropriate mechanical ventilation may induce hemodynamic alterations through cardiopulmonary interactions. The aim of this study was to explore the relationship between airway pressure and central venous pressure during the first 72 h of mechanical ventilation and its relevance to patient outcomes. We conducted a r...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894020970363
更新日期:2020-11-25 00:00:00
abstract::Increased exposure to ambient particulate matter (PM) is associated with elevated morbidity and mortality in patients with cardiopulmonary diseases and cancer. We and others have shown that PM induces lung microvascular barrier dysfunction which potentially enhances the systemic toxicity of PM. However, the mechanisms...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/689906
更新日期:2017-07-01 00:00:00
abstract::Pharmacokinetic studies with oral treprostinil demonstrate that three times daily (TID) dosing reduces peak-to-trough plasma trepostinil fluctuations compared with twice daily (BID) dosing. TID dosing may allow for faster titration, higher total daily doses, and potentially improve the tolerability of oral trepostinil...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018770654
更新日期:2018-04-01 00:00:00
abstract::Uncorrected atrial septal defect undergoes right ventricle chronic volume overload which may lead to pulmonary hypertension and Eisenmenger Syndrome. The soluble suppression of tumorigenicity-2 is a left ventricle strain biomarker; however, its role in right ventricle strain is unclear. This study aimed to investigate...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894020915832
更新日期:2020-05-26 00:00:00
abstract::Despite the discovery more than 15 years ago that patients with hereditary pulmonary arterial hypertension (HPAH) inherit BMP type 2 receptor ( BMPR2) mutations, it is still unclear how these mutations cause disease. In part, this is attributable to the rarity of HPAH and difficulty obtaining tissue samples from patie...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018765840
更新日期:2018-04-01 00:00:00
abstract::A loss of K+ efflux in pulmonary arterial smooth muscle cells (PASMCs) contributes to abnormal vasoconstriction and PASMC proliferation during pulmonary hypertension (PH). Activation of high-conductance Ca2+-activated (BK) channels represents a therapeutic strategy to restore K+ efflux to the affected PASMCs. However,...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/688838
更新日期:2016-12-01 00:00:00
abstract::Pulmonary embolism is associated with high rates of mortality and morbidity. It is important to understand direct comparisons of current interventions to differentiate favorable outcomes and complications. The objective of this study was to compare ultrasound-accelerated thrombolysis versus systemic thrombolysis versu...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894020953724
更新日期:2020-09-28 00:00:00
abstract::Low-grade albuminuria, determined by the urinary albumin to creatinine ratio, has been linked to systemic vascular dysfunction and is associated with cardiovascular mortality. Pulmonary arterial hypertension is related to mutations in the bone morphogenetic protein receptor type 2, pulmonary vascular dysfunction and i...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018824564
更新日期:2019-04-01 00:00:00
abstract::Infection, thrombosis, and catheter dislodgment are well-recognized potential complications of chronic intravenous prostanoid therapy for pulmonary arterial hypertension. As long-term outcomes of pulmonary hypertension patients improve, novel adverse events are likely to arise. We describe the sudden development of un...
journal_title:Pulmonary circulation
pub_type:
doi:10.1177/2045893217748054
更新日期:2018-01-01 00:00:00