ITTBioMed’s Post

The OptimAT study is one of the largest study conducted in hospitalized patients under antithrombotics with the purpose to validate PBPK and PopPK models in this population. Until the release of the PBPK models for DOACs these next days in the same journal edited by the American Society for Clinical Pharmacology & Therapeutics, I am very proud to present you this paper made in collaboration with the Lausanne team (Frédéric Gaspar Monia Guidi Chantal Csajka) about the PopPK model for apixaban. Here are the paper's highlights: 📣 Renal function and P-gp activity are the main factors affecting apixaban concentration in our cohort of hospitalized patients. 📣 The study's results challenge the current recommendation for standardized periprocedural management of anticoagulants in patients with renal impairment and reduced P-gp activity. 📣 A priori adjustment of dosage regimen according to moderate and severe renal function and monitoring of apixaban plasma concentrations might be beneficial in specific situations, such as periprocedural management of polymorbid and/or polymedicated patients. Model-informed precision dosing is getting closer to bedside ! https://lnkd.in/efEKPVxm #pharmacology #pharmacometrics #precisionmedicine #poppk

Multiple sclerosis (MS) is a chronic inflammatory disease that, due to autoimmune mechanisms, initially causes the destruction of the myelin sheath of central nervous system axons, and subsequently, axonal dysfunction. Different clinical courses have been described for MS, with the most common being relapsing-remitting MS (RRMS). These are episodes of flare-ups separated by periods of complete or incomplete recovery and are related to approximately 80% of cases. There are various treatment options for MS, including injectable drugs (interferons and glatiramer acetate) and oral agents such as fingolimod and teriflunomide (TFN). TFN reversibly inhibits the dihydroorotate dehydrogenase enzyme, which is required for the proliferation of activated lymphocytes. Therefore, fewer lymphocytes are available to cross the blood-brain barrier. Several side effects, including the elevation of hepatic enzymes, lymphopenia and neutropenia, hypertension, and gastrointestinal discomfort, have been reported. Among the newly suspected rare complications is the increased risk of thrombosis and vascular accidents in patients with MS. In the following clinical case report, the authors present the rare case of a middle-aged woman with RRMS presenting with an acute ischemic stroke after prescription of teriflunomide. 👉 https://lnkd.in/edhc5caH #Acuteischemicstroke#Adverseeffects#Multiplesclerosis#Teriflunomide

Interesting study assessing the risk of QT-interval at therapeutic doses of mitiperstat, a myeloperoxidase inhibitor in clinical development for treatment of patients with heart failure and preserved or mildly reduced ejection fraction, NASH and COPD. Read full article Pharmacology Research & Perspectives : https://lnkd.in/gTyKXp8h #pharmacokinetics #cardiovascularhealth #mitiperstat #Phase1Study #heartfailure #drugsafety #healthcare #NASH #COPD #clinicaldevelopment

We've reached a key milestone in our mission to develop innovative treatments for chronic airway diseases, with the completion of a proof of pharmacology study for our lead asset, EP395. It showed a positive effect on inflammation and epithelial function in LPS-challenged healthy volunteers. This supports our preclinical data and reinforces EP395's potential as a groundbreaking treatment. We're now looking forward to the results of our Phase 2a study in COPD patients, due early next year. Our CMO Ginny Norris commented, “The results from this study support our hypothesis that EP395 can affect both inflammation and epithelial function, which is key for treating COPD and other inflammatory diseases of the lung.” To find out more about the study, please visit our website: https://lnkd.in/eN5qr47M #EP395 #Innovation #HealthcareResearch #COPD #MedicalAdvancements #Inflammation #RespiratoryHealth

𝐍𝐨𝐫𝐭𝐡𝐒𝐞𝐚 𝐓𝐡𝐞𝐫𝐚𝐩𝐞𝐮𝐭𝐢𝐜𝐬 𝐈𝐧𝐢𝐭𝐢𝐚𝐭𝐞𝐬 𝐏𝐡𝐚𝐬𝐞 𝟐𝐚 𝐓𝐫𝐢𝐚𝐥 𝐟𝐨𝐫 𝐎𝐫𝐳𝐢𝐥𝐨𝐛𝐞𝐧 𝐢𝐧 𝐈𝐅𝐀𝐋𝐃 NorthSea Therapeutics B.V. (‘NST’) NorthSea Therapeutics announces the dosing of the first patient in its Phase 2a clinical trial of Orziloben (NST-6179) for intestinal failure-associated liver disease (IFALD), a condition affecting individuals on prolonged intravenous nutrition. The trial is a randomized, double-blind, Phase 2a, placebo-controlled study conducted across North America, evaluating Orziloben's safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) in adult subjects with IFALD. The readout is anticipated in H2 2025. IFALD is characterized by hepatic inflammation, cholestasis, and steatosis, primarily affecting patients receiving prolonged parenteral nutrition, with hepatic fibrosis being a major concern. Preclinical studies show Orziloben's efficacy in preventing severe cholestasis, fibrosis, and liver damage in PN-induced liver injury models. Professor Palle Bekker Jeppesen Palle Bekker Jeppesen from Rigshospitalet in Copenhagen highlights Orziloben's potential as a therapeutic option for IFALD patients. Rob de Ree Rob de Ree, NST’s CEO, emphasizes their commitment to advancing innovative treatments for liver diseases and the potential impact of Orziloben in addressing this unmet medical need. #LiverDisease #ClinicalTrial #MedicalResearch #HealthcareInnovation #IFALD #NASH #Orziloben #Biotech #TreatmentDevelopment #HealthTech

How do #BileAcids play a crucial role in the development of cardiometabolic, autoimmune, and neoplastic diseases? Why did the most clinically developed #BileAcid candidate fail FDA approval, and more importantly, is there a way to salvage #BileAcid drug discovery? Does a hidden goldmine for both novel druggable targets and therapeutic strategies exist within #BileAcid signaling cascades? I am incredibly excited to share my first first-author publication entitled "Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets", which was published in Nature's Signal Transduction and Targeted Therapy #STTT (Impact Factor: 39.3). https://lnkd.in/eeXqqcsT As I approach my graduation from St. John's University College of Pharmacy and Health Sciences in three weeks with my #PharmD I reflect on this paper as a capstone project. In which, I am proud to showcase the key tools of a pharmacist that I have had the privilege to fall in love with over the last six years: biochemistry, physiology, pharmacology, medicinal chemistry, pharmaceutics, and clinical pharmacotherapeutics. I could not be more grateful to my mentor Sunil Kumar, Ph.D. for his guidance and support throughout this 1.5-year journey. Keep posted, many, many more to come soon! #FXR #TGR5 Intercept Pharmaceuticals #ObeticholicAcid #Ocaliva Madrigal Pharmaceuticals #Resmetirom #Rezdiffra #Biochemistry #Physiology #Pharmacology #FDA #NASH #NAFLD #T2DM #ASCVD

As the primary tissue for maintaining glucose homeostasis, skeletal muscle cells/glucose uptake pathways are potential therapeutic targets for type 2 diabetes. Here, Ham et al. from Monash Institute of Pharmaceutical Sciences describe a role of G protein-coupled receptor kinases (GRKs) in β2-adrenoceptor-mediated glucose uptake. Read more in February issue of Pharmacology Research & Perspectives 👉 https://lnkd.in/gAU9E36k #pharmacology #pharmacologyresearch #pharmacologyeducation

The FDA approves Madrigal Pharmaceuticals’ Rezdiffra for Metabolic dysfunction-Associated #SteatoHepatitis (#MASH), previously known as NASH, marking a milestone in treating fatty liver disease. #Rezdiffra targets lipid metabolism and shows promising results in clinical trials. The FDA’s decision relied partly on a phase 3 trial published in the New England Journal of Medicine (➡️DOI: 10.1056/NEJMoa2309500⬅️). Biopsy analysis of over #900 individuals revealed that after 12 months of treatment, the 25% of patients presented reduction in both lipids accumulation and inflammation without worsening fibrosis, in contrast to around 10% on placebo. Additionally, approximately 25% of patients experienced #fibrosis improvement without making fatty liver symptoms worse, compared to 14% in the placebo group. 👁️👁️𝐑𝐞𝐳𝐝𝐢𝐟𝐟𝐫𝐚 𝐚𝐥𝐬𝐨 𝐝𝐞𝐦𝐨𝐧𝐬𝐭𝐫𝐚𝐭𝐞𝐝 𝐞𝐧𝐡𝐚𝐧𝐜𝐞𝐦𝐞𝐧𝐭𝐬 𝐢𝐧 𝐥𝐨𝐰-𝐝𝐞𝐧𝐬𝐢𝐭𝐲 𝐥𝐢𝐩𝐨𝐩𝐫𝐨𝐭𝐞𝐢𝐧 #𝐜𝐡𝐨𝐥𝐞𝐬𝐭𝐞𝐫𝐨𝐥 𝐥𝐞𝐯𝐞𝐥𝐬.👁️👁️ By Gabriele Imperato, Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, University of Milan. https://lnkd.in/dJ7UhSf7 Valentina Ravetta