Gastrointestinal disease and drug metabolism
Orally administered medications must dissolve and go into solution in the GI tract before absorption across the gut wall into circulating blood. These processes depend upon many factors, including:4
- lipid solubility
- concentration of nonionized molecules
- gastric blood flow
- gastric emptying time
- gut pH
- timing of meals
- meal content
- bowel length
GI diseases that alter these factors may therefore affect drug absorption and disposition.
In addition to playing a role in absorption, the GI tract also contributes to drug metabolism. For example, two enzymes that are found in the gut, alcohol dehydrogenase and CYP 3A4, contribute to xenobiotic metabolism.
It is difficult to perform prospective trials in patients with acute GI disease. For example, it would be hard to study the pharmacokinetics and pharmacodynamics of a drug in a patient with diarrhea secondary to influenza. Even those with chronic GI diseases may have confounding factors that make pharmacokinetic and pharmacodynamic evaluation difficult.
Adapted from: Garnett WR. Gastrointestinal and hepatic disease. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;63-74.
With permission from Elsevier (www.elsevier.com).
