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". 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 pharmacokinetic effects of the intestinal microbiome have never been asked about in the CICM Part I or Part II exams, and an ICU trainee may go through their entire career without really needing to know this material, which renders the act of reading about it only slightly less pointless than the act of writing about it in a supposedly exam-oriented website. In spite of these concerns, what follows is a substantial exploration of enterohepatic recirculation and the effect of gut flora on the bioavailability of orally administered drugs.
Cummings and Macfarlane (1997) estimate that bacteria account for about 65% of the dry weight of the content of the caecum. They are not inert bystanders but rather highly active participants, and there is a lot of them. They hydrolyse, dehydroxylate, decarboxylate, dealkylate, dehalogenate, deaminate, reduce, aromatise and oxidise. The end result may be:
Orme (1984) offers sulphasalazine as a good example. The drug itself is completely inactive, but is metabolised by gut bacteria to produce sulphapyridine and 5-amino salicylic acid (which have a therapeutic effect).
However, the most important bacterial contribution is probably hydrolysis of the glucuronide conjugates which are excreted in the bile. This is mediated by the glucronidase enzyme of the bacterial microflora. The effect of this reaction is the restoration of availability to a drug which you'd thought you were rid of. Again, the intestine will reabsorb the drug and it will have another pass through first-pass metabolism. This is one of the reasons we have multi-dose charcoal. Drugs which undergo extensive enterohepatic recirculation are listed below.
The 30-page opus in honor of this process by Roberts et al (2002) is a monumental work and to do it justice would require several chapters. In short: