a b/aiagents4pharma/talk2knowledgegraphs/tests/files/adalimumab.md 

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1. Drug Name





  
  

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    Adalimumab





  
  

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2. Mechanism of Action (MoA)





  
  

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    Adalimumab is a fully human monoclonal antibody (IgG1) that specifically binds to tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine. By neutralizing TNF-α, Adalimumab reduces inflammation and prevents immune-mediated tissue damage, making it effective in treating inflammatory bowel diseases such as Crohn’s disease (CD) and ulcerative colitis (UC).





  
  

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3. Pharmacokinetics





  
  

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    Absorption: Administered subcutaneously (SC), reaching peak plasma concentration in approximately 4–6 days.





  
  

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    Distribution: Exhibits a biphasic distribution with high specificity for TNF-α.





  
  

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    Metabolism: Degraded via proteolysis in the reticuloendothelial system.





  
  

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    Excretion: Eliminated mainly via intracellular catabolism, as monoclonal antibodies are not excreted through the liver or kidneys.





  
  

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4. ADME (Absorption, Distribution, Metabolism, Excretion)





  
  

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    Absorption: Bioavailability of approximately 64% after SC administration.





  
  

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    Distribution: Volume of distribution (Vd) is 4.7–6 L, with extensive binding to TNF-α.





  
  

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    Metabolism: Degraded into peptides and amino acids by proteolytic enzymes.





  
  

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    Excretion: Eliminated via reticuloendothelial and lymphatic systems, not through renal or hepatic pathways.





  
  

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5. Biodistribution





  
  

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    Primarily found in plasma and extracellular fluids, targeting inflamed intestinal tissue in IBD patients.





  
  

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    Crosses the placental barrier, but FcRn-mediated clearance reduces fetal exposure.





  
  

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    Minimal penetration into the central nervous system (CNS) due to its large molecular size.





  
  

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6. Target Binding





  
  

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    High specificity and affinity for TNF-α (~0.1 nM binding affinity).





  
  

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    Inhibits both soluble and transmembrane TNF-α, preventing its interaction with TNF receptors.





  
  

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    Reduces downstream pro-inflammatory signaling cascades, such as NF-κB and MAPK pathways.





  
  

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7. Pharmacodynamics





  
  

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    Reduces pro-inflammatory cytokine production, including IL-1, IL-6, and interferon-γ.





  
  

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    Decreases leukocyte migration and adhesion, preventing tissue damage in the gastrointestinal (GI) tract.





  
  

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    Improves mucosal healing, reducing disease severity in Crohn’s disease and ulcerative colitis.





  
  

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    Onset of action: Effects observed within 2–4 weeks, with sustained response in long-term therapy.





  
  

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8. Abbreviations





  
  

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    IBD – Inflammatory Bowel Disease





  
  

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    TNF-α – Tumor Necrosis Factor-alpha





  
  

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    SC – Subcutaneous





  
  

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    NF-κB – Nuclear Factor Kappa B





  
  

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    MAPK – Mitogen-Activated Protein Kinase





  
  

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    FcRn – Neonatal Fc Receptor





  
  

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    CD – Crohn’s Disease





  
  

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    UC – Ulcerative Colitis





  
  

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References





  
  

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    https://pubmed.ncbi.nlm.nih.gov/24831559/





  
  

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    https://www.cghjournal.org/article/S1542-3565%2813%2901050-1/fulltext





  
  

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    https://www.mdpi.com/2077-0383/12/22/7132





  
  

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