Search Results (4)

Abnormal corneal wound healing can compromise corneal transparency and lead to visual impairment. Mineralocorticoid receptor antagonists (MRA) are promising candidates to promote corneal remodeling with anti-inflammatory properties and lack gluococorticoids-associated side effects. In this preclinical study, a new polymer-free hydroxypropyl-gamma-cyclodextrin-based eyedrop containing 0.1% spironolactone (SPL), a potent but non-water-soluble MRA, was investigated for its ocular surface tolerance and efficacy in a rat model of corneal wound healing. SPL eyedrops were stable for up to 9 months at 4 °C. The formulation was well-tolerated since no morphological changes or inflammatory reactions were observed in the rat cornea after multiple daily instillations over 7 days. SPL eyedrops accelerated rat corneal wound healing, reduced corneal edema and inflammation, enhanced epithelial integrity, and improved nerve regeneration, suggesting restoration of corneal homeostasis, while potassium canrenoate, an active and soluble metabolite of SPL, had no effect. SPL eyedrops could benefit patients with impaired corneal wound healing, including that secondary to glucocorticoid therapy. Repurposing known drugs with known excipients will expedite translation to the clinic. Full article

In March 2020, the World Health Organization (WHO) announced a global pandemic of coronavirus disease 2019 (COVID-19) that presented mainly as an acute infection of the lower respiratory tract (pneumonia), with multiple long-term consequences, including lung fibrosis. The aim of this study was to evaluate the influence of potassium canrenoate on inflammatory markers in the treatment of COVID-19 pneumonia. A randomized clinical trial (RCT) of intravenous potassium canrenoate vs. placebo was performed between December 2020 and November 2021. This study is a secondary analysis of that RCT. In the final analysis, a total of 49 hospitalized patients were included (24 allocated to the potassium canrenoate group and 25 to the placebo group). Patients were assessed by serum testing and blood cell cytometry on day 1 and day 7 of the intervention. Age, sex, and body mass index were not significantly different between the placebo group and intervention group. Although there was a significantly higher rate of ischemic heart disease in the placebo group, rates of other preexisting comorbidities were not significantly different. There were no significant differences in the inflammatory parameters between the potassium canrenoate and placebo groups on day 1 and day 7. However, the intragroup comparisons using Wilcoxon’s test showed significant differences between day 1 and day 7. The CD3% for potassium canrenoate increased significantly between day 1 and day 7 (12.85 ± 9.46; 11.55 vs. 20.50 ± 14.40; 17.80; p = 0.022), while the change in the placebo group was not significant (15.66 ± 11.39; 12.65 vs. 21.16 ± 15.37; 16.40; p = 0.181). The IL-1ß total count [%] increased over time for both potassium canrenoate (0.68 ± 0.58; 0.45 vs. 1.27 ± 0.83; 1.20; p = 0.004) and placebo (0.61 ± 0.59; 0.40 vs. 1.16 ± 0.91; 1.00; p = 0.016). The TNF-α total count (%) decreased significantly between day 1 and day 7 for potassium canrenoate (0.54 ± 0.45; 0.40 vs. 0.25 ± 0.23; 0.10; p = 0.031), but not for placebo (0.53 ± 0.47; 0.35 vs. 0.26 ± 0.31; 0.20; p = 0.056). Interleukin-6 (pg/mL) showed a significant decrease between day 1 and day 7 for potassium canrenoate (64.97 ± 72.52; 41.00 vs. 24.20 ± 69.38; 5.30; p = 0.006), but not the placebo group. This RCT has shown that the administration of potassium canrenoate to patients with COVID-19-induced pneumonia may be associated with significant changes in certain inflammatory markers (interleukin-6, CD3%, TNF-α), potentially related to pulmonary fibrosis. Although some positive trends were observed in the potassium canrenoate group, none of these observations reached statistical significance. Any possible benefits from the use of potassium canrenoate as an anti-inflammatory or antifibrotic drug in COVID-19 patients require further investigation. Full article

In December 2019 the SARS-CoV-2 virus appeared in the world, mainly presenting as an acute infection of the lower respiratory tract, namely pneumonia. Nearly 10% of all patients show significant pulmonary fibrotic changes after the infection. The aim of this study was to evaluate the effectiveness and safety of potassium canrenoate in the treatment of COVID-19-associated pneumonia and pulmonary fibrosis. We performed a randomized clinical trial (RCT) of potassium canrenoate vs placebo. A total of 55 patients were randomized and 49 were included in the final analysis (24 allocated to the intervention group and 25 allocated to the control group). Patients were assessed by physical examination, lung ultrasound, CT imaging and blood samples that underwent biochemical analysis. This RCT has shown that the administration of potassium canrenoate to patients with COVID-19 induced pneumonia was not associated with shorter mechanical ventilation time, shorter passive oxygenation, shorter length of hospitalization or less fibrotic changes on CT imaging. The overall mortality rate was not significantly different between the two groups. Adverse events recorded in this study were not significantly increased by the administration of potassium canrenoate. The negative outcome of the study may be associated with the relatively small number of patients included. Any possible benefits from the use of potassium canrenoate as an antifibrotic drug in COVID-19 patients require further investigation. Full article

In March 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared a global pandemic by the World Health Organization (WHO). The clinical course of the disease is unpredictable but may lead to severe acute respiratory infection (SARI) and pneumonia leading to acute respiratory distress syndrome (ARDS). It has been shown that pulmonary fibrosis may be one of the major long-term complications of COVID-19. In animal models, the use of spironolactone was proven to be an important drug in the prevention of pulmonary fibrosis. Through its dual action as a mineralocorticoid receptor (MR) antagonist and an androgenic inhibitor, spironolactone can provide significant benefits concerning COVID-19 infection. The primary effect of spironolactone in reducing pulmonary edema may also be beneficial in COVID-19 ARDS. Spironolactone is a well-known, widely used and safe anti-hypertensive and antiandrogenic medication. It has potassium-sparing diuretic action by antagonizing mineralocorticoid receptors (MRs). Spironolactone and potassium canrenoate, exerting combined pleiotropic action, may provide a therapeutic benefit to patients with COVID-19 pneumonia through antiandrogen, MR blocking, antifibrotic and anti-hyperinflammatory action. It has been proposed that spironolactone may prevent acute lung injury in COVID-19 infection due to its pleiotropic effects with favorable renin–angiotensin–aldosterone system (RAAS) and ACE2 expression, reduction in transmembrane serine protease 2 (TMPRSS2) activity and antiandrogenic action, and therefore it may prove to act as additional protection for patients at highest risk of severe pneumonia. Future prospective clinical trials are warranted to evaluate its therapeutic potential. Full article