Table 2.

Drug delivery considerations with general surgical bowel procedures

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