scholarly journals Sildenafil 4.0—Integrated Synthetic Chemistry, Formulation and Analytical Strategies Effecting Immense Therapeutic and Societal Impact in the Fourth Industrial Era

2021 ◽  
Vol 14 (4) ◽  
pp. 365
Author(s):  
Andreas Ouranidis ◽  
Anastasia Tsiaxerli ◽  
Elisavet Vardaka ◽  
Catherine K. Markopoulou ◽  
Constantinos K. Zacharis ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Clinical Applications ◽  
Reversible Inhibitor ◽  
Societal Impact ◽  
Routes Of Administration ◽  
Administration Routes ◽  
The Us ◽  
Analytical Strategies ◽  
Pulmonary Arterial ◽  
Phosphodiesterase Type

Sildenafil is a potent selective, reversible inhibitor of phosphodiesterase type 5 (PDE5) approved for the treatment of erectile dysfunction and pulmonary arterial hypertension. Whilst twenty years have passed since its original approval by the US Food and Drug Administration (USFDA), sildenafil enters the fourth industrial era catalyzing the treatment advances against erectile dysfunction and pulmonary hypertension. The plethora of detailed clinical data accumulated and the two sildenafil analogues marketed, namely tadalafil and vardenafil, signify the relevant therapeutic and commercial achievements. The pharmacokinetic and pharmacodynamic behavior of the drug appears complex, interdependent and of critical importance whereas the treatment of special population cohorts is considered. The diversity of the available formulation strategies and their compatible administration routes, extend from tablets to bolus suspensions and from per os to intravenous, respectively, inheriting the associated strengths and weaknesses. In this comprehensive review, we attempt to elucidate the multi-disciplinary elements spanning the knowledge fields of chemical synthesis, physicochemical properties, pharmacology, clinical applications, biopharmaceutical profile, formulation approaches for different routes of administration and analytical strategies, currently employed to guide the development of sildenafil-based compositions.

scholarly journals Exploring the binding mechanisms of PDE5 with chromeno[2,3-c]pyrrol-9(2H)-one by theoretical approaches

RSC Advances ◽  
2018 ◽  
Vol 8 (53) ◽  
pp. 30481-30490 ◽  
Author(s):  
Xianfeng Huang ◽  
Peng Xu ◽  
Yijing Cao ◽  
Li Liu ◽  
Guoqiang Song ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Pulmonary Arterial Hypertension ◽  
Drug Target ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Theoretical Approaches ◽  
Pulmonary Arterial ◽  
Phosphodiesterase Type ◽  
Binding Mechanisms ◽  
Important Drug

Cyclic nucleotide phosphodiesterase type 5 (PDE5) is exclusively specific for the cyclic guanosine monophosphate (cGMP), and PDE5 is an important drug target for the treatment of erectile dysfunction and pulmonary arterial hypertension (PAH).

scholarly journals Avanafil for the treatment of erectile dysfunction: initial data and clinical key properties

2012 ◽  
Vol 5 (1) ◽  
pp. 35-41 ◽  
Author(s):  
George T. Kedia ◽  
Stefan Ückert ◽  
Farhang Assadi-Pour ◽  
Markus A. Kuczyk ◽  
Knut Albrecht
Keyword(s):  
Erectile Dysfunction ◽  
Initial Data ◽  
Treatment Options ◽  
Pharmacokinetic Profile ◽  
Phase Iii ◽  
Onset Of Action ◽  
Number Of Patients ◽  
First Choice ◽  
The Us ◽  
Phosphodiesterase Type

Orally active, selective inhibitors of phosphodiesterase type 5 (PDE 5, cyclic GMP PDE), such as sildenafil, tadalafil and vardenafil, are currently the first-choice treatment options for the clinical management of erectile dysfunction (ED) of various etiologies and severities. However, a significant number of patients remain dissatisfied with the available therapies due a lack of efficacy or discomfort arising from adverse events. Several new PDE5 inhibitors, among which are avanafil (TA-1790), lodenafil, mirodenafil, udenafil, SLX-2101, JNJ-10280205 and JNJ-10287069, have recently been approved and introduced into the market or are in the final stages of their clinical development. Avanafil (marketed in the US under the brand name STENDRA™) has been developed by VIVUS Inc. (Mountain View, CA, USA) and has recently received approval from the US Food and Drug Administration (FDA) for use in the treatment of male ED. The drug has demonstrated improved selectivity for PDE5, is rapidly absorbed after oral administration with a fast onset of action and a plasma half-life that is comparable to sildenfil and vardenafil. In phase II and phase III clinical trials that included a large number of patients, avanafil has been shown to be effective and well tolerated. Owing to its favorable pharmacodynamic and pharmacokinetic profile, avanafil is considered as a promising new option in the treatment of ED. The present article summarizes the initial data and clinical key properties of avanafil.

Synthesis of isotope – labeled selective PDE5 inhibitor sildenafil (UK 92480-10)

2018 ◽  
Vol 106 (10) ◽  
pp. 851-855
Author(s):  
R. Sekhar Bolla ◽  
Kali Charan Gulipalli ◽  
N. Murthy Gandikota ◽  
Srinu Bodige ◽  
I. V. Kasi Viswanath
Keyword(s):  
Erectile Dysfunction ◽  
Pulmonary Arterial Hypertension ◽  
Pde5 Inhibitor ◽  
Cyclic Guanosine Monophosphate ◽  
Selective Inhibitor ◽  
Guanosine Monophosphate ◽  
Isotopic Abundance ◽  
Pulmonary Arterial ◽  
Phosphodiesterase Type ◽  
Male Erectile Dysfunction

Abstract Sildenfil a vasodilating agent is a selective inhibitor of cyclic guanosine monophosphate – specific phosphodiesterase type 5 which is used for the treatment of male erectile dysfunction and pulmonary arterial hypertension. We presented a detailed approach for the synthesis of [2H3]sildenafil, [2H8]sildenafil and N-desmethyl [2H8]sildenafil. By using the approach we successfully synthesized [2H3]sildenafil, [2H8]sildenafil and N-desmethyl [2H8]sildenafil with good isotopic abundance.

scholarly journals Pulmonary Hypertension Complicating Pregnancy

2021 ◽  
Author(s):  
Sheila Krishnan ◽  
Erin M. Fricke ◽  
Marcos Cordoba ◽  
Laurie A. Chalifoux ◽  
Reda E. Girgis
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Post Partum ◽  
Severe Heart Failure ◽  
Neonatal Morbidity ◽  
Risk Of Death ◽  
Risk Condition ◽  
Pulmonary Arterial ◽  
Phosphodiesterase Type ◽  
Type V

Abstract Purpose of review This study aims to describe the pathophysiology of pregnancy in pulmonary hypertension (PH) and review recent literature on maternal and fetal outcomes. Recent findings There is an increasing number of pregnant women with PH. Maternal mortality in pulmonary arterial hypertension (PAH) ranges from 9 to 25%, most commonly from heart failure and arrythmias. The highest risk of death is peri-partum and post-partum. Fetal/neonatal morbidity and mortality are also substantial. There are high rates of prematurity, intrauterine growth retardation, and preeclampsia. Women should be referred to expert centers for management. Combination PAH therapy with parenteral prostacyclin and a phosphodiesterase type V inhibitor is recommended. Induced vaginal delivery is preferred, except in cases of severe heart failure or obstetric indications for cesarean section. Summary Despite advances in management, pregnancy in PAH remains a high-risk condition and should be prevented.

scholarly journals Biodistribution of Mesenchymal Stromal Cells after Administration in Animal Models and Humans: A Systematic Review

2021 ◽  
Vol 10 (13) ◽  
pp. 2925
Author(s):  
Manuel Sanchez-Diaz ◽  
Maria I. Quiñones-Vico ◽  
Raquel Sanabria de la Torre ◽  
Trinidad Montero-Vílchez ◽  
Alvaro Sierra-Sánchez ◽  
...  
Keyword(s):  
Animal Models ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cellular Therapy ◽  
The Body ◽  
Intralesional Injection ◽  
Intraarterial Infusion ◽  
Routes Of Administration ◽  
Administration Routes

Mesenchymal Stromal Cells (MSCs) are of great interest in cellular therapy. Different routes of administration of MSCs have been described both in pre-clinical and clinical reports. Knowledge about the fate of the administered cells is critical for developing MSC-based therapies. The aim of this review is to describe how MSCs are distributed after injection, using different administration routes in animal models and humans. A literature search was performed in order to consider how MSCs distribute after intravenous, intraarterial, intramuscular, intraarticular and intralesional injection into both animal models and humans. Studies addressing the biodistribution of MSCs in “in vivo” animal models and humans were included. After the search, 109 articles were included in the review. Intravenous administration of MSCs is widely used; it leads to an initial accumulation of cells in the lungs with later redistribution to the liver, spleen and kidneys. Intraarterial infusion bypasses the lungs, so MSCs distribute widely throughout the rest of the body. Intramuscular, intraarticular and intradermal administration lack systemic biodistribution. Injection into various specific organs is also described. Biodistribution of MSCs in animal models and humans appears to be similar and depends on the route of administration. More studies with standardized protocols of MSC administration could be useful in order to make results homogeneous and more comparable.

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