Effect of gastric motility on drug absorption

This chapter answers parts from Section B(ii) of the 2023 CICM Primary Syllabus, which expects the exam candidate to "Describe the absorption of drugs and factors that influence this". Though absorption has appeared in the previous exam papers,  most often the college will ask about the factors which influence oral absorption (eg. Question 20 from the first paper of 2014 and Question 5(p.2) from the first paper of 2010). The focus is usually not on gastric motility. However, gastric motility is one of the most important influences on drug absorption and oral bioavailability. Because it is affected by critical illness and shock, it would also play a role in determining how critical illness in general affects pharmacokinetics (which was the topic of Question 5 from the first Fellowship paper of 2011).  

In summary:

  • The rate of gastric emptying affects all drugs, even those which are well absorbed in the stomach.
  • This is because the small intestine has a significantly larger surface area and contributes the most to drug absorption.
  • Ergo, gastric motility is a major determinant of oral drug absorption.

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Effect of gastric motility on drug absorption

Few drugs are absorbed in the stomach. Theoretically the low pH of the gastric fluid should render all but the most acidic drugs into a lipid-soluble nonpolar form, which would favour absorption. However, this is usually not the case for two main reasons. Firstly, the stomach lining is coated with a thick protective mucus which makes diffusion difficult. Secondly, the stomach has a fairly small surface area when compared to the small bowel. The consequences of this are that the stomach participates minimally in drug absorption, and any situation which involves drugs sitting in the stomach for a long time will result in poor drug bioavailability.

Thus, gastric emptying rate is one of the main determinants of oral drug bioavailability and gastrointestinal drug absorption. If the stomach does not empty, practically nothing is going to get absorbed. Even drugs which are undissociated in gastric acid and fully dissociated in the small bowel are still predominantly absorbed in the small bowel because of its comparatively massive surface area.

In brief summary, gastric emptying can be affected by:

  • Food in the stomach (especially fat)
  • Viscosity of the stomach content
  • Size of the tablet or capsule 
  • Sedation 
  • Mobility
  • Abdominal compartment pressure
  • Gastric perfusion
  • Autonomic and hormonal activity
  • Anticholinergic drugs

Food in the stomach seems to be the main determinant. In case you are ever confronted with the question "how quickly should gastric emptying take place", you may turn to Davis et al (1986) whose team fed radiolabelled pellets to people and found that on an empty stomach they emptied within minutes. However, "a heavy breakfast resulted in greatly delayed empyting and in one study the units were retained in the stomach in all six subjects for at least nine hours"



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