This chapter answers parts from Section B(ii) of the 2017 CICM Primary Syllabus, which expects the exam candidate to "Describe absorption and factors that will influence it". 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). As gastric absorption plays only a minor role in the total oral bioavailability of drugs, reading a prolonged discussion of it will be unlikely to be a major influence on exam success. The time-poor candidate can safely omit this section in favour of memorising tables, which seems to be the college's favoured strategy in adult education. 

In summary, drug absorption in the stomach is usually a minor player in the total absorption of a drug dose. This is because the stomach has a smaller surface area, and the drug usually does not spend very long in there (see the section on gastric motility). Moreover some drugs are ionised by gastric pH and do not absorb very well (i.e. they are less lipid soluble in that state). Some drugs are actually inactivated (degraded) by gastric pH, which reduces their absorption. 

Drug characteristics which favour gastric absorption

To be well absorbed in the stomach, a drug would need to be:

  • A small molecule
  • Weakly acidic (pKa higher than the pH of stomach acid)
  • Highly concentrated (i.e. a large dose of drug)

Additional caveats in the ICU environment:

  • The drug may be highly concentrated because of overdose
  • The gastric pH may be high because of routine use of proton pump inhibitors
  • The gastric mucus layer may be thin because of critical illness
  • Bypassing the stomach altogether (jejunal administration, gastric sleeve or bypass surgery etc)

Empirically, it is possible to demonstrate that there are a few drugs which will still be absorbed to some small extent even when the stomach is uselessly immobile. Mostly, these are the theoretically predicted weakly acidic drugs which are fully un-dissociated in the presence of normal gastric pH. In fact pKa seems to be one of the major determinants of absorption through the stomach wall. To study these phenomena usually animals either have their pylorus ligated, or have an exteriorised patch of gastric mucosa (a "Pavlov pouch").  In the graph presented below, Schanker et al (1957) were able to demonstrate that acidic drugs with pKa over 2.0 were absorbed much better than bases in the artificially acidified stomach of the anaesthetised rat. 

absorption of drugs from the stomach according to pKa - Shanker, 1957

This rat study and a subsequent human follow-up by Hogben Adrian and Schanker (1957) laid down that main tenet of gastric pharmacokinetics ("passive transfer at a rate determined by the ionisation and lipid solubility of the drug molecules") as repeated in Rang and Dale.

Apart from being lipid-soluble, another factors which favour drug absorption in the stomach is sufficiently high concentration gradient to drive simple passive diffusion. This means the drug has to be low-potency (i.e. given as a very large dose). It also helps when the drug has a very small molecule, which facilitates diffusion across the gastric mucus layer. All of these criteria are met by ethyl alcohol. It is a small lipophilic molecule, and one needs to take tens of grams in order to see any effect (which sets up a nice steep concentration gradient). This was first demonstrated by Sven Berggren and Leonard Goldberg in 1940, in some slightly intoxicated cats (10ml/kg of 5% solution was used, which equates to approximately three beers).

Drugs which are well absorbed in the stomach

Apart from ethanol, there is a handful of other drugs which will be absorbed from the stomach in spite of very poor gastric emptying. Hogben and Adrian (1957) noted that "salicylic acid, aspirin, thiopental, secobarbital and antipyrine, which are undissociated in the acidic gastric contents, were readily absorbed"  and that surprisingly many drugs "may be absorbed by the human stomach as rapidly or more rapidly than ethyl alcohol". Knowing this list of gastrically absorbed drugs has some relevance for the intensive care community, as our patients are notoriously lazy at emptying their stomachs (being critically ill, affected by shock and ileus and whatnot).

Drugs which are Well Absorbed in the Stomach
  • Ethanol
  • Aspirin
  • Paraquat
  • Thiopentone
  • Caffeine
  • Warfarin
  • Phenytoin
  • Theophylline

This of course does not mean that these drugs get absorbed predominantly from the stomach; it means that in a rat with a ligated pylorus they still are able to traverse the gastric mucosa with relative ease. This has the implication that when given down an NG tube in a patient with poor gut transit, they will still be absorbed to some extent.

Interestingly, some authors list paracetamol among the substances with high gastric absoprtion rates, whereas others use it as a marker of gastric emptying precisely because of poor gastric absorption. This may actually have something to do with the delivery vehicle. A drug formulation designed to stay in the stomach for a longer period of time will obviously enjoy more gastric absorption than the same drug formulated to exit the stomach rapidly. Hypothetically, if the patient were to swallow a large rubbery blob of highly fatty paracetamol-rich goo, it would sit in their stomach for hours, and the majority of paracetamol in ther bloodstream would come from their stomach. That goo would then be called a gastroretentive delivery system (Gupta & Singh, 2012), and there are several examples of drugs which take advantage of such delivery mechanisms:

Gupta & Singh (2012) go on to discuss the various ways one can promote gastric retention of the substance, including having it stick to the gastric mucosa like a limpet, expanding hideously to a size much larger than the pyloric outlet, floating like a little raft on the gas-fluid level in the gastric fundus, and various other inventive methods. Of these, there are several which are relavant to formulations of paracetamol. For instance, Nethaji et al (2017) describe paracetamol delivery as mucoadhesive microspheres. Interestingly, this method was actually being promoted to decrease the rate of absorption, ironing out the rapid toxic peak in mucosal and blood concentrations which might result from overmuch gastric dumping. 


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