With regard to ORAL drug dosing, describe the factors that affect the fraction of drug reaching the systemic circulation (80% marks). How may these factors be altered in a patient with shock (20% marks)?
For a good answer candidates were expected to define bioavailability and the factors
that affected a drugs oral bioavailability. This was often overlooked by candidates.
For example, factors affecting absorption (Metabolism by gut flora, drug / drug
interactions with in the gut, lipophilicity and hydrophilicity of the drug (drug that are
markedly lipophilic or hydrophilic cross the mucus layer or villous membrane poorly),
First Pass clearance and sites and mechanism of possible metabolism, to define
hepatic clearance, extraction ratio (providing a formula proved helpful to many
candidates) and factors that affected hepatic drug clearance. Candidates often
lacked an understanding of this area, or failed to mention it. In relation to the second
part of the question, candidates were expected to mention the effects of reduced
absorption and altered first pass metabolism resulting in uncertain bioavailability of
Syllabus: Section II, 2a, b
References: Pharmacology, Rang, Ritter and Dale, Chp 7. Goodman and Gilman's
the Pharmacological Basis of Therapeutics, Chp 1
It is weird that the college wanted a definition of bioavailability in their model answer, when they themselves had paraphrased that definition in the question. The definition of bioavailability according to Birkett et al (2009):
"Bioavailability is the fraction of the dose which reaches systemic circulation as intact drug"
This one is from Pharmacokinetics Made Easy, which is the official pharmacokinetics text of the CICM primary exam. A better definition from the FDA, created by consensus of pharmacologists, reads "bioavailability is the rate and extent to which the active drug ingredient or therapeutic moiety is absorbed from a drug product and becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action". But that doesn't really roll off the tongue, and is harder to remember.
Factors which affect bioavailability include:
Generic influences on drug absorption
Factors affecting gastrointestinal absorption
Factors affecting first pass metabolism
The effect of shock on these factors:
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.