Question 20

Describe the factors affecting drug absorption from the gastrointestinal tract

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College Answer

This is a very broad and open question. While a structured approach was useful, a sound 
knowledge of first principles or even being able to “think on the fly” would have provided 
candidates with enough opportunities to generate a pass.


Being able to "think on the fly" is of course a commendable quality, but one might have expected more from mid-stage ICU trainees. One should be able to come up with something more than just an off-the-cuff response. A structured approach would have benefited from a tabulated format and from the separation of issues into "drug factors" and "site factors", all of which play a role.  

The following model answer was concocted from Martinez & Amidon (2002),  Orme (1984) and "Drug absorption from the gastrointestinal tract" - Chapter 5 (p87) from Basic Pharmacokinetics, by Jambhekar and Breen. It is impossible to guess what was on the college marking sheet, but it must have been something similar to this.

Factors which Influence Drug Absorption from the Gastrointestinal Tract

Drug factors: 

  • Concentration

A large drug dose will be absorbed more rapidly because of the high concentration gradient

  • Molecule size

Small molecules diffuse more easily

  • pKa

Weak acids are better absorbed; lipophilic drugs are better absorbed

  • Tablet disintegration

Stability of the tablet determines the dispersion rate of the drug, and therefore the rate of absorption. This is manipulated intentionally in slow release formulations

  • Particle size

The smaller the particles, the greater the surface area from which the drug will be eluted

Gastrointestinal factors

Gastric emptying is the major determinant of absorption

  • Intestinal motility

Intestinal motility can increase or decrease absorption (eg. slow gut transit can ensure complete absorption of a drug bezoar)

  • Splanchnic perfusion

Gut perfusion is a rate-limiting step in drug absorption only for rapidly absorbed drugs, but as perfusion slows it also becomes more important for all other drugs.

  • Surface area

Surface area of the small intestine is massive (usually, tens of square metres) and this increases absorption. Factors which decrease intestinal surface area (eg. denuded villi due to gastroenteritis, or surgacal short gut) will decrease drug absorption

  • Mode of transport

Drugs can be transported by passive diffusion (either paracellular or transcellular); some are actively transported out of the gut lumen, and others may be actively excreted back into it by efflux pumps.

  • Intestinal content

Interaction with other drugs and food substances (eg. tetracycline chelating intestinal calcium from milk, thereby forming an insoluble complex which defeats absorption) 

  • Bile and bile salts

The emulsifying effect of bile is critical to the absorption of fat-soluble vitamins and steroids

  • Enterohepatic recirculation

Some drugs may be eliminated in the bile only to be reabsorbed in the jejunum

  • Gut bacteria

Gut bacteria may either deactivate drugs (by metabolisng them) or activate drugs (by metabolism of an inactive precursor). 

  • Metabolism in the intestinal wall

Enterocytes may metabolise drugs before they undergo first-pass metabolism. Injured enterocytes (eg. after ischaemia) may lose their metabolic function.


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