Table 2.
Surgical issue | Physiological impact | Drug delivery considerations |
---|---|---|
Short bowel syndrome |
▪ Occurs following large resections of the small bowel (usually greater than 50%) ▪ May lead to significant impairment in the absorption of water, electrolytes, and nutrients ▪ Can alter luminal pH and transit times, reduce small chain fatty acid digestion, and impair regulation of the ileal brake ▪ Gastric hypersecretion may increase the acid load delivered to the duodenum |
▪ May cause inefficient disintegration and drug release from formulations that are dependent on gastrointestinal transit time, leading to reduce efficacy ▪ Reduction in duodenal pH may delay drug release from formulations that have pH-responsive coatings or matrices that are designed to release drug into the small intestine for optimal absorption |
Resection of the terminal ileum |
▪ May reduce the ileal brake and cause rapid intestinal transit ▪ Can cause choleretic diarrhea, due to the terminal ileum being responsible for bile salt reabsorption |
▪ May reduce the time available for drug absorption from both oral and rectal dosage forms ▪ May cause inefficient release of drugs from formulations that are dependent on gastrointestinal transit time ▪ Diarrhea can affect other physiological factors in the gastrointestinal tract (e.g., intestinal volume, pH, mucosal integrity, and resident microbiome) |
Resection of the colon | ▪ Colonic resections may alter the local microenvironment and physiology of the gastrointestinal tract |
▪ May cause inefficient release of drugs from formulations that are dependent on gastrointestinal transit time ▪ May affect pH-dependent dosage forms that utilize the drop in pH on entry into the colon ▪ May affect formulations that exploit the metabolic capabilities of the colonic microbiome |
Surgical intervention for rectal cancer | ▪ May cause functional complications that increase intestinal motility and transit (e.g., urgency and frequent bowel movements) |
▪ May reduce the time available for drug absorption ▪ May cause inefficient release of drugs from formulations that are dependent on gastrointestinal transit time ▪ Diarrhea can affect other physiological factors in the gastrointestinal tract (e.g., intestinal volume, pH, mucosal integrity, and resident microbiome) |
Intestinal stoma |
▪ An ileostomy produces a relatively continuous stream of liquid and semi-solid material ▪ Can significantly change the absorption of water and electrolyte in the gastrointestinal tract, leading to a relatively high output ▪ Patients are at risk for developing electrolyte depletion (e.g., hyponatremia) and dehydration ▪ Colostomy tends to produce more formed stool and less risk of metabolic disturbances |
▪ Can affect the release of drugs from formulations that are dependent on pH and transit time (e.g., enteric-coated and sustained-release formulations) ▪ Use of immediate-release formulations are preferred to improve drug absorption in patients, especially those with an ileostomy |