924: SLX-2101, A New Long-Acting PDE5 Inhibitor: Preliminary Safety, Tolerability, PK and Endothelial Function Effects in Healthy Subjects

Prince, William; Campbell, Ayanna; Tong, Warwick; Sweetnam, Paul M.; Willett, Michael S.; Roesch, Benno; García, Wilson; Rosen, Raymond C.; Goldstein, Irwin

doi:10.1016/s0022-5347(18)33160-4

Cited by 12 publications

(9 citation statements)

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“…The duration of action of the "combination" (i.e., SLx-2101 andSLx-2081) was approximately 48 h. SLx-2101 has shown high potency, with therapeutic concentrations sustained for more than 24 h . A randomized, double-blind, single-dose study was performed in healthy volunteers, who received one of five doses: 5, 10, 20, 40, or 80 mg (Donabedian et al, 2006;Prince et al, 2006). Positive effects on penile rigidity were observed approximately 24 h after administration at doses of 20, 40, and 80 mg. No clinically significant adverse CV effects were recorded at these doses.…”

Section: Drugs For Nonintracavernosal Administrationmentioning

confidence: 99%

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

Andersson

2011

Pharmacological Reviews

315

326

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Section: Drugs For Nonintracavernosal Administrationmentioning

confidence: 99%

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

Andersson

2011

Pharmacological Reviews

315

326

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“…This drug has a long-lasting duration of inhibition of PDE5, at least 36 -48 h at all doses studied. Single doses of SLx-2101 exhibited safety and tolerability in healthy volunteers and it is a candidate for once-daily dosing [55] . SLx-2101 exhibited enhanced potency in preclinical molecular and cellular rat model studies, lasting longer than 24 h [56] .…”

Section: New-generation Pde5 Inhibitorsmentioning

confidence: 99%

Novel phosphodiesterase-5 (PDE5) inhibitors in the alleviation of erectile dysfunction due to diabetes and ageing-induced oxidative stress

Gür

Sikka

2008

Expert Opinion on Investigational Drugs

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Background : Diabetes and ageing are associated with erectile dysfunction (ED). Under these conditions, increased oxidative stress produces superoxide ions, which in turn suppresses the nitric oxide-cyclic guanosine monophosphate pathway. The phophodiesterase-5 (PDE5) inhibitors still remain ineffective in 15 -57% of impotent men. Objective : To identify the efficacy of conventional and novel PDE5 inhibitors on oxidative stress involved in diabetes and ageing. Methods : An electronic search of the literature was conducted to review published information relating diabetes and ageing to ED and to cover latestage developments of novel PDE5 inhibitors. Results/conclusion : Safe and more efficacious alternatives that can modulate PDE5 levels in ED regarding oxidative stress conditions are needed. Included in this review are updates on the new PDE5 inhibitors avanafil, udenafil, SLx-2101, and mirodenafil.

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“…SLx-2101, a novel phosphodiesterase type 5 (PDE-5) inhibitor for hypertension, had previously been assessed in Phase I/II studies using an Immediate Release (IR) tablet formulation which failed to meet the target PK profi le due to C max -related adverse events, and C 24 falling below the effi cacious plasma concentration threshold [ 49 ]. In order to reduce the peak-trough ratio and thereby improve the safety profi le and ensure once-daily dosing, an MR tablet was required to deliver a PK profi le within the therapeutic window.…”

Section: Product Optimisation Using a Two Dimensional Design Spacementioning

confidence: 99%

Approaches to Rapid In Vivo Optimization of Hydrophilic Matrix Tablets

McDermott

Scholes

Lin

et al. 2014

Hydrophilic Matrix Tablets for Oral Controlled Release

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An effective hydrophilic matrix tablet must deliver a stable stream of active compound at an optimal rate to the gastrointestinal (GI) tract in order to achieve a benefi cial therapeutic effect. It must do this whilst moving through the GI tract, passing through a range of different environments, and experiencing environmental changes in pH, fl uid volume, fl uid composition, and physical forces, whilst also accounting for regional changes in drug absorption.In addition to this variable environment, the physico-chemical and biopharmaceutical properties of new drugs (or NCE, "new chemical entities") emerging from the industry R&D pipeline increasingly possess suboptimal solubility [ 1 ] and and/ or permeability characteristics which have an infl uence on the drug delivery. When tasked with developing a hydrophilic matrix tablet formulation, the development team must therefore rationalise these many parameters in order to meet the target product profi le (TPP).Traditional formulation development studies involve expensive and timeconsuming screening of multiple prototypes in preclinical species, in order to identify a limited number of "lead" systems to then take forward into human clinical pharmacokinetic (PK) studies (Fig. 9.1 ). This process can cost over $1.5M and take 12-15 months [ 2 ].

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924: SLX-2101, A New Long-Acting PDE5 Inhibitor: Preliminary Safety, Tolerability, PK and Endothelial Function Effects in Healthy Subjects

Cited by 12 publications

References 0 publications

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

Novel phosphodiesterase-5 (PDE5) inhibitors in the alleviation of erectile dysfunction due to diabetes and ageing-induced oxidative stress

Approaches to Rapid In Vivo Optimization of Hydrophilic Matrix Tablets

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