Lecture 7 - Drug metabolism and eliminiation (the liver)

• Enteral drug delivery

  Administration of drugs via the oral route, which then pass through the gastrointestinal (GI) tract
• Enteral drug delivery

  • Convenient method for drug administration
  • Allows for systemic effects as the drug reaches circulation
  • Can lead to first pass metabolism in the liver, causing low bioavailability of the drug
• First pass metabolism


  Enteral drugs drain directly to the liver before entering systemic circulation, leading to drug inactivation or conversion to more polar metabolites
• Parenteral drug delivery


  Administration through other routes other than the GI tract, such as intravenous, intramuscular, subcutaneous, cutaneous, inhalation, sublingual and rectal
• Parenteral drug delivery


  • Intravenous injection is the most direct systemic delivery method
  • Intramuscular and subcutaneous injections also allow for systemic effects, albeit with varying speeds of drug absorption
  • Cutaneous administration is used when systemic effects are not required and allows for slow sustained release of lipid-soluble drugs
  • Inhalation is used for volatile or gaseous drugs such as anaesthetics, and can cause systemic effects or deliver drugs for local lung effects
  • Sublingual administration bypasses first pass metabolism by directly absorbing drugs into the systemic circulation beneath the tongue
  • Rectal administration allows for systemic delivery as a significant portion of rectal blood avoids first pass liver metabolism, making it useful for local drug delivery and systemic effects
• Some drugs can leave the body via alternative routes, such as through the lungs or hepatobiliary system secretion into bile
• Phase 1 metabolism


  Involves the functionalisation of drugs by introducing chemically reactive groups through oxidation, reduction and hydrolysis
• Phase 2 metabolism


  Involves the conjugation of drugs with polar groups such as sugars or amino acids to make them more water-soluble and easily excreted
• Parenteral drug delivery methods bypass the GI tract and liver, thus avoiding first pass metabolism
• Enterohepatic circulation


  • Involves the recycling of drugs metabolites through the liver and intestine
  • Liver metabolites drugs to polar glucuronate conjugates, which are excreted in bile and reabsorbed in the intestine, contributing to the drug recycling
  • This process limits fecal drug excretion and ensures that drugs are mostly reabsorbed rather than being excreted in feces, with some exceptions for certain drugs and in individuals with kidney failure