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.

Discussion

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

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.

Branson, Herman. "The kinetics of reactions in biological systems." Archives of biochemistry and biophysics 36.1 (1952): 48-59.

Dost, F. H. "Absorption, Transit, Occupancy und Availments als neue Begriffe in der Biopharmazeutik." Journal of Molecular Medicine 50.8 (1972): 410-412.

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

Rescigno, Aldo. "Bioequivalence." Pharmaceutical research 9.7 (1992): 925-928.

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

Allam, Ahmed N., S. S. El Gamal, and V. F. Naggar. "Bioavailability: A pharmaceutical review." Int J Novel Drug Deliv Tech 1.1 (2011): 77-93.

Pond, Susan M., and Thomas N. Tozer. "First-pass elimination basic concepts and clinical consequences." Clinical pharmacokinetics 9.1 (1984): 1-25.

De Paepe, Peter, Frans M. et al "Pharmacokinetic and pharmacodynamic considerations when treating patients with sepsis and septic shock." Clinical pharmacokinetics 41.14 (2002): 1135-1151.

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