Combination therapy with Bosentan and Sildenafil improves Raynaud’s phenomenon and fosters the recovery of microvascular involvement in systemic sclerosis

Bellando-Randone, Silvia; Lepri, Gemma; Bruni, Cosimo; Blagojević, Jelena; Radicati, A.; Cometi, Laura; Paulis, Amato de; Matucci‐Cerinic, Marco; Guiducci, Serena

doi:10.1007/s10067-015-3119-3

Cited by 26 publications

(27 citation statements)

References 23 publications

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“…The aforementioned drugs were distributed in two compartments of the tablet of either immediate or sustained release. Similarly to hypertension, clinical reports, not only on PAH but also on Raynaud's disease, suggest that the combination of PDE-5 inhibitors and BOS can improve the effectiveness of therapy; therefore, the thermal properties of SIL, TA and BOS are investigated in details in the present study (6,11). Thermal decomposition of sildenafil citrate was already described by Melnikov et al (23).…”

Section: Thermal Propertiesmentioning

confidence: 84%

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Physicochemical Properties of Bosentan and Selected PDE-5 Inhibitors in the Design of Drugs for Rare Diseases

et al. 2016

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Abstract.The study provides the physicochemical characteristic of bosentan (BOS) in comparison to tadalafil (TA) and sildenafil citrate (SIL). Despite some reports dealing with thermal characteristic of SIL and TA, physicochemical properties of BOS have not been investigated so far. Recent clinical reports have indicated that the combination of bosentan and PDE-5 inhibitor can improve the effectiveness of pharmacotherapy of pulmonary arterial hypertension (PAH). However, in order to design personalized medicines for therapy of chronic rare diseases, detailed information on the thermal behaviour and solubility of each drug is indispensable. Thus, XRD, DSC and TGA-QMS analyses were applied to compare the properties of the drugs, their thermal stability as well as to identify the products of thermal degradation. The dehydration of BOS started at 70°C and was followed by the chemical degradation with the onset at 290°C. The highest thermal stability was stated for TA, which decomposed at ca. 320°C, whereas the lowest onset of the thermal decomposition process was stated for SIL, i.e. 190°C. The products of the drug decomposition were identified. FT-FIR was applied to study intra-and intermolecular interactions between the drug molecules. FT-MIR and Raman spectroscopy were used to examine the chemical structure of the drugs. Chemoinformatic tools were used to predict the polar surface area, pKa, or logP of the drugs. Their results were in line with solubility and dissolution studies.

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Section: Thermal Propertiesmentioning

confidence: 84%

“…TA (6). Furthermore, it has been reported that BOS combined with SIL has been found effective in the therapy of Raynaud's phenomenon (11).…”

Section: Introductionmentioning

confidence: 95%

Physicochemical Properties of Bosentan and Selected PDE-5 Inhibitors in the Design of Drugs for Rare Diseases

et al. 2016

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“…PDE5 inhibitors potentiate NO‐dependent vasodilation by prolonging the elevation of cGMP. Sildenafil is under active study in a variety of conditions associated with microvascular dysfunction 31, 32, 33, 34. Sildenafil's endothelial repair properties have been studied in several conditions associated with chronic diabetes 34.…”

Section: Introductionmentioning

confidence: 99%

Phosphodiesterase‐5 inhibition potentiates cerebrovascular reactivity in chronic traumatic brain injury

Kenney

Amyot

Moore

et al. 2018

Ann Clin Transl Neurol

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BackgroundTraumatic cerebrovascular injury (TCVI), a common consequence of traumatic brain injury (TBI), presents an attractive therapeutic target. Because phosphodiesterase‐5 (PDE5) inhibitors potentiate the action of nitric oxide (NO) produced by endothelial cells, they are candidate therapies for TCVI. This study aims to: (1) measure cerebral blood flow (CBF), cerebrovascular reactivity (CVR), and change in CVR after a single dose of sildenafil (ΔCVR) in chronic TBI compared to uninjured controls; (2) examine the safety and tolerability of 8‐week sildenafil administration in chronic symptomatic moderate/severe TBI patients; and as an exploratory aim, (3) assess the effect of an 8‐week course of sildenafil on chronic TBI symptoms.MethodsForty‐six subjects (31 chronic TBI, 15 matched healthy volunteers) were enrolled. Baseline CBF and CVR before and after administration of sildenafil were measured. Symptomatic TBI subjects then completed an 8‐week double‐blind, placebo‐controlled, crossover trial of sildenafil. A neuropsychological battery and neurobehavioral symptom questionnaires were administered at each study visit.ResultsAfter a single dose of sildenafil, TBI subjects showed a significant increase in global CVR compared to healthy controls (P < 0.001, d = 0.9). Post‐sildenafil CVR maps showed near‐normalization of CVR in many regions where baseline CVR was low, predominantly within areas without structural abnormalities. Sildenafil was well tolerated. Clinical Global Impression (CGI) scale showed a trend toward clinical improvement while on sildenafil treatment.FindingsSingle‐dose sildenafil improves regional CVR deficits in chronic TBI patients. CVR and ΔCVR are potential predictive and pharmacodynamic biomarkers of PDE5 inhibitor therapy for TCVI. Sildenafil is a potential therapy for TCVI.

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“…Of note, a significant improvement of capillaroscopic findings was observed in SSc patients treated with bosentan alone or with a combination of bosentan and sildenafil after 3 and 6 months with reduction of the “late” and “active” phase “scleroderma” pattern and an increase of the “aspecific” findings or “early” pattern . Thus, the “reverse” order of appearance of the capillaroscopic changes is obviously possible and is currently observed after treatment with immunosuppressive drugs, hematopoietic stem cell transplantation and bosentan …”

Section: Discussionmentioning

confidence: 92%

“…21 Thus, the "reverse" order of appearance of the capillaroscopic changes is obviously possible and is currently observed after treatment with immunosuppressive drugs, hematopoietic stem cell transplantation and bosentan. [21][22][23][24] Further research on precise interpretation of the dynamics of capillaroscopic changes in SSc is necessary eg, could "reverse" ap-…”

Section: Patientmentioning

confidence: 99%

Inhomogeneity of capillaroscopic findings in systemic sclerosis

Lambova

Müller‐Ladner

2019

Int J of Rheum Dis

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Background Despite the great interest in capillaroscopy in systemic sclerosis (SSc), research on the possible combinations of different microvascular phenomena at different fingers in SSc patients have not been performed until now. Objective To assess the diversity of capillaroscopic findings in SSc. Methods The study includes analysis of the capillaroscopic findings in 40 SSc patients who were divided into the following categories: “scleroderma”, type pattern ‐ “early”, “active”, “late” phase, normal and/or nonspecific findings. The data were analyzed using descriptive statistics and t test. Results In 77% of the patients, inhomogeneity of the capillaroscopic findings of the fingers was detected. The most frequent combinations of capillaroscopic patterns were “early + active” (n = 7), “active + late” phase (n = 7), “active” phase + normal and/or nonspecific findings (n = 6), “early + active” phase + normal and/or nonspecific findings (n = 4). Concomitant presence of normal and/or nonspecific findings and “late” phase was detected in only 3 cases. Conclusion Inhomogeneity of the capillaroscopic findings in SSc is a frequent phenomenon. The results indicate that combinations of “scleroderma” type capillaroscopic findings from different phases could be observed as well as concomitant appearance of pathological and normal/or nonspecific findings of different digits. This phenomenon could be a result of the complex action of different factors eg, disease duration, severity of Raynaud's phenomenon, presence of digital ulcers, local action of different angiogenic and angiostatic factors, gradual transition from one phase to another due to the extensive capillary area, therapeutic interventions.

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Combination therapy with Bosentan and Sildenafil improves Raynaud’s phenomenon and fosters the recovery of microvascular involvement in systemic sclerosis

Cited by 26 publications

References 23 publications

Physicochemical Properties of Bosentan and Selected PDE-5 Inhibitors in the Design of Drugs for Rare Diseases

Physicochemical Properties of Bosentan and Selected PDE-5 Inhibitors in the Design of Drugs for Rare Diseases

Phosphodiesterase‐5 inhibition potentiates cerebrovascular reactivity in chronic traumatic brain injury

Inhomogeneity of capillaroscopic findings in systemic sclerosis

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