pharmacokinetics 3

• Major routes of administration


  • Enteral routes (via the GI system)
  • Par-enteral Routes (not via GI system)
• Enteral routes

  • Sublingual
  • Buccal
  • Oral
  • Rectal
• Par-enteral Routes (Injection routes)


  • Intramuscular (i.m.)
  • Subcutaneaous (s.c.)
  • Intravenous (i.v.)
  • Intradermal (ID)
  • Intrathecal (IT)
• Par-enteral Routes (Application to other epithelial surfaces)


  • Skin (transdermal/topical)
  • Cornea
  • Vagina
  • Nasal mucosa
• Enteral Routes of Administration: Venous blood flow not to hepatic portal vein
• Enteral Routes of Administration: Rectal venous blood avoids HPV, Reducing first pass metabolism!, Venous blood flow
• Bioavailability


  The proportion of the drug in a dosage form available to the body.
• i.v injection gives 100% bioavailability F=1.0
• Bioavailability says nothing about effectiveness!
• Oral bioavailability


  1. Dose

  2. Destroyed in gut

  3. Not absorbed

  4. Destroyed by gut wall

  5. Destroyed by liver to systemic circulation
• Bioavailability factor (F) for digoxin


  • 1.0 for parenterally administered (i.v.)
  • 0.77 for elixir (solution/suspension)
  • 0.62 for tablets
• Digoxin


  a cardiac glycoside used for treatment of congestive heart failure
• Factors affecting oral absorption


  • Compliance: Taking medication regularly (forgetting to take medication)
  • Drug formulation - disintegration/ dissolution rates (particle size) Tablets, elixir, slow or sustained release
  • Presence of food - e.g. penicillin (can bind Ca2+ ions in dairy products) / dilution
  • pH of gastric contents – antacids, PPI's
  • Metabolism within the GIT or mucosa.
  • Gastrointestinal motility / disease
  • Migraine and diabetic neuropathy cause stasis and slow drug absorption
  • Diarrhoea: increases motility and reduces absorption (oral contraceptives!)
  • Crohn's disease and coeliac disease (gluten allergy) reduce absorptive capacity!
• Parenteral Administration


  ADVANTAGES: avoids acid and enzymes of the GI-tract, ABSORPTION: more predictable than by mouth, easy to titrate dose more accurately

  DISADVANTAGES: Often requires trained personnel, Sterile equipment, Patient acceptability, more expensive and potentially hazardous than via the enteral route.
• Parenteral Routes (Injection) Summary


  • Intradermal: Rich in antigen presenting cells, Only small volume
  • Subcutaneous: Small volume
  • intravenous: High bioavailability, Large volume
  • Intra arterial: Rapid onset, large volume
  • Intramuscular: Medium volume and can act as a depot storage.
• Intra-arterial (central line) is rarely used unless in hospital setting, Risk of gangrene due to vasoconstriction
• Epidural: Local anaesthesia, eg. lignocaine, does not enter CNS, Introduced between L3/L4 or L4/L5 (below termination of spinal cord)
• Lumbar Puncture (spinal tap): Remove CSF for analysis, administer antibiotics and some anti-cancer agents eg. gentamicin, cephalosporine, Allows passage across the BBB.
• Topical Advantages

  • Drugs applied to skin, ear, mucous membranes of the eye, nose, throat and vagina are generally given for local effects.
  • Easy to administer.
  • Avoids first pass metabolism and acid/enzymes.
• Topical Disadvantages


  • Difficult to regulate absorption (properties change with age),
  • Systemic side effects: eg topical creams and lotions (NSAID's ibuprofen), misoprostol/NO patches for male erectile dysfunction (MED).
• Transdermal / Percutaneous


  Used for peripheral distribution, Drug passes across the epidermis and into the blood vessels of the dermis, drug absorption is most rapid in areas where skin is thin (scrotum, face and scalp) these are usually avoided!
• Transdermal / Percutaneous Advantages


  • Drugs applied transdermally given for peripheral effects.
  • Easy to administer.
  • Skin is rate limiting, avoids first pass metabolism and acid/enzymes, no GI irritation.
• Transdermal / Percutaneous Disadvantages


  • Difficult to regulate absorption.
• Transdermal / Percutaneous Examples


  • Scopolamine (motion sickness)
  • Oestradiol (oestrogen replacement therapy)
  • Nicotine (stop smoking alternative)
  • Buprenorphine (opioid analgesic)