Define bioavailability. Outline the factors which affect it.

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College Answer

Many candidates did not specify that bioavailability describes the proportion/fraction of drug
reaching the systemic circulation (to differentiate from the portal circulation). Some candidates
considered only factors impacting absorption from the GI tract or stated that bioavailability
related only to orally administered drugs. Candidates failed to provide an equation, or got
equations or graphs wrong. Nearly all candidates failed to provide a comprehensive list of
factors affecting bioavailability.

Discussion

This question is similar to Question 5(p.2) from the first paper of 2010, which specifically asked for factors which influence oral bioavailability. This time, the question was broader in scope, and the exam candidates (clearly doing the past papers for preparation) were taken aback by this.

Definition of bioavailability:

  • Bioavailability is the fraction of the dose which reaches systemic circulation intact.
    It is described by this equation:
    simple bioavailability equation
  • 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

References

References

Wesch, Roland. "Absolute and relative bioavailability." Drug Discovery and Evaluation: Methods in Clinical Pharmacology. Springer Berlin Heidelberg, 2011. 173-180.

Vaughan, D. P. "A model-independent proof of Dost's law of corresponding areas." Journal of pharmacokinetics and biopharmaceutics 5.3 (1977): 271-276.

Balant, L. P. "Is there a need for more precise definitions of bioavailability?." European Journal of Clinical Pharmacology 40.2 (1991): 123-126.

Koch-Weser, Jan. "Bioavailability of drugs." New England Journal of Medicine 291.10 (1974): 503-506.