Bezafibrate 200mg tablets

Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive bile duct damage and cholestasis. While ursodeoxycholic acid (UDCA) is the first-line therapy, approximately 40% of patients have incomplete responses, necessitating alternative treatments. This systematic review and meta-analysis evaluate the efficacy and safety of novel oral anti-cholestatic agents for PBC. Methods: A systematic literature search was conducted in electronic databases up to September 2024. Randomized controlled trials, cohort studies, and case-control studies evaluating novel oral anti-cholestatic agents in adult PBC patients were included. The primary outcome was a change in alkaline phosphatase (ALP) levels. Safety was assessed by the incidence of serious adverse events. Random-effect meta-analyses were performed. Results: Ten studies involving 878 patients were analyzed. Novel agents included seladelpar, fenofibrate, saroglitazar, bezafibrate, elafibranor, and budesonide. The meta-analysis showed significant reductions in ALP levels with novel agents compared to the controls (SMD −2.80; 95% CI −3.56, −2.03; p < 0.00001), with high heterogeneity (I2 = 93%). Saroglitazar achieved the largest effect size. There was no significant difference in serious adverse events between novel agents and controls (OR 1.21; 95% CI 0.81, 1.83; p = 0.35). Conclusions: Novel oral anti-cholestatic agents show promise in improving biochemical markers in PBC patients with suboptimal UDCA responses, with a safety profile comparable to controls. However, study heterogeneity and limited long-term data restrict direct comparisons. Larger standardized trials with extended follow-up are needed to confirm long-term efficacy and safety.

Abstract licence: CC BY

The most documented fibrates are gemfibrozil, clofibrate and bezafibrate, while for statins, the majority of the published literature focuses on atorvastatin and simvastatin. The present work reviews previously published research concerning the effects of these hypocholesterolaemic pharmaceuticals on fish, with a particular focus on commercially important species, commonly produced by the European aquaculture industry, specifically in recirculated aquaculture systems (RAS). Overall, results suggest that both acute and chronic exposures to lipid-lowering compounds may have adverse effects on fish, disrupting their capacity to excrete exogenous substances, as well as both lipid metabolism and homeostasis, causing severe ontogenetic and endocrinological abnormalities, leading to hampered reproductive success (e.g., gametogenesis, fecundity), and skeletal or muscular malformations, having serious repercussions on fish health and welfare. Nonetheless, the available literature focusing on the effects of statins or fibrates on commonly farmed fish is still limited, and further research is required to understand the implications of this matter on aquaculture production, global food security and, ultimately, human health.

Abstract licence: CC BY

Aim. To conduct a generalization of scientific research on the history of the use of medications for the correction of dyslipidemia in clinical practice. Materials and methods. The analysis and generalization of scientific articles, guidelines and recommendations on the justification and implementation of the appointment of hypolipidemic drugs for the treatment and prevention of cardiovascular diseases (CVD) was carried out. The methods used were: systematic approach, bibliosemantic, analytical. Results. Hypotheses regarding the role of hypercholesterolemia in the development of atherosclerotic lesions of the cardiovascular system were proposed as early as the second half of the 19th century, and scientific approaches regarding the need to correct dyslipidemia were substantiated only with the introduction of the concept of risk factors in the second half of the 20th century. However, it took almost two decades for the introduction of hypolipidemic drugs for the prevention and treatment of CVD into clinical practice. The first pharmacological drug that began to be used in clinical practice was nicotinic acid (niacin). Bile acid sequestrants (cholestyramine, colestipol, colesevelam) became the second group, and fibrates (fenofibrate, bezafibrate, gemfibrozil, and ciprofibrate) became the third group of hypolipidemic therapy drugs. Later, these drugs gave way to statins, whose clinical effectiveness was higher and the safety profile was better. Statin therapy is generally well tolerated and adverse reactions occur in less than 5% of randomized clinical trials. At the current stage, statins remain first-line drugs for the correction of lipid metabolism. The evidence base for statins is significant, and the results of randomized clinical trials have demonstrated the effectiveness of this group of drugs in the secondary and primary prevention of CVD. Since the end of the 90s of the 20th century, there has been a steady increase in the prescription of statins in clinical practice. Сonclusions. Medications for the correction of dyslipidemia have been used in clinical practice since the second half of the 20th century. Niacin, fibrates, and bile acid sequestrants have now been replaced by statins, which remain the first-line drugs for the correction of lipid metabolism.

Abstract licence: CC BY-NC

Pharmaceuticals and microplastics constitute potential hazards in aquatic systems, but their combined effects and underlying toxicity mechanisms remain largely unknown. In this study, a simultaneous characterization of bioaccumulation, associated metabolomic alterations and potential recovery mechanisms was performed. Specifically, a bioassay on Mediterranean mussels (Mytilus galloprovincialis) was carried out with polyethylene microplastics (PE-MPLs, 1 mg/L) and citalopram or bezafibrate (500 ng/L). Single and co-exposure scenarios lasted 21 days, followed by a 7-day depuration period to assess their potential recovery. PE-MPLs delayed the bioaccumulation of citalopram (lower mean at 10 d: 447 compared to 770 ng/g dw under single exposure), although reaching similar tissue concentrations after 21 d. A more limited accumulation of bezafibrate was observed overall, regardless of PE-MPLs co-exposure (<MQL-3.2 ng/g dw). Metabolic profiles showed a strong effect of pharmaceuticals, generally independent of PE-MPLs co-exposure. Alterations of the citrate cycle (bezafibrate exposure) and steroid and prostaglandin metabolism (citalopram and bezafibrate exposures) were highlighted. PE-MPLs alone also impacted metabolic pathways, such as neurotransmitters or purine metabolism. After depuration, relevant latent or long-lasting effects were demonstrated as, for instance, the effect of citalopram on neurotransmitters metabolism. Altogether, the observed molecular-level responses to pharmaceuticals and/or PE-MPLs may lead to a dysregulation of mussels' reproduction, energy metabolism, and/or immunity.

Abstract licence: CC BY