Question 15

Define bioavailability (10% of marks). Outline the factors which affect it (90% of marks).

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College Answer

Many candidates spent time defining and describing aspects of pharmacokinetics which were not relevant to the question. E.g. clearance, volume of distribution and half-life. Candidates who scored well utilised a structure which incorporated the headings of the factors which affect the bioavailability of medications with a simple description as to the nature of the effect. These factors included: the physical properties of the drug, the preparation, patient factors, the route of administration and metabolism amongst others.


  • Bioavailability is the fraction of the dose which reaches systemic circulation intact
    • IV bioavailability is by definition 100%
    • "Absolute" bioavailability compares one non-IV route with IV administration. 
    • "Relative" bioavailability compares one non-IV route or formulation with another (instead of using IV route as a reference).
    • Bioavailability is measured using the area under the concentration-time curve (Dost's Law). The ratio of AUCs is the bioavailability value.
Factors which Influence Drug Bioavailability

Generic influences on drug bioavailability

  • Drug concentration at site of administration
  • Surface area of the absorptive site
  • Drug pKa
  • Drug molecule size
  • pH of the surrounding fluid

Factors affecting first pass metabolism

  • Drug absorption from the gut
  • Drug metabolism in the gut
  • Metabolism in the gut wall
  • Metabolism in bloodstream (eg. plasma esterases)
  • Hepatic blood flow
  • Hepatic enzyme activity
  • Spontaneous drug degradation

Factors affecting gastrointestinal absorption

  • Gastric motility
  • Intestinal motility
  • Splanchnic perfusion
  • Tablet disintegration
  • Mode of transport
  • Intestinal content
  • Bile and bile salt content
  • Enterohepatic recirculation
  • Metabolism by gut bacteria
  • Metabolism in the intestinal wall
  • Drug on drug interactions in the gut
  • First pass metabolism

Bioavailability via transdermal and mucosal routes of administration

  • Mucosal blood flow
  • Drug lipophilicity
  • Factors affecting membrane penetration, eg. molecule size, pKa, etc
  • pH of the mucosal fluid


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