Multiple disease states can significantly influence the oral drug absorption process by affecting blood flow and the functionality of the gastrointestinal (GI) system. Various GI diseases, including conditions that alter GI motility, such as diarrhea, decreased acid secretions (achlorhydria), and infections, have been associated with reduced drug absorption.

Substances such as alcohol and specific drugs, including antineoplastics, can also negatively impact drug absorption. For instance, alcohol can affect absorption by impacting drug motility and interacting with the drug itself. It damages the gastrointestinal mucosa and alters enzyme and transporter functions. On the other hand, antineoplastic drugs reduce absorption by harming rapidly dividing intestinal cells, leading to decreased surface area for uptake. Celiac disease, characterized by damage to the villi in the small intestine, decreases absorptive surface area and alters gastric emptying and intestinal activity. This change impairs the absorption of several drugs, such as antibiotics, acetaminophen, and practolol. Crohn's disease, marked by transmural inflammation, compromises intestinal integrity, leading to a modified drug absorption process. Congestive heart failure reduces the heart's pumping efficiency, results in decreased blood flow to the GI tract, and induces intestinal edema. This condition diminishes the absorption of oral drugs like loop diuretics.

Liver disorders, notably cirrhosis, impair portal blood flow and first-pass metabolism of drugs, thereby increasing their systemic circulation and bioavailability. As a result, toxicity risks for some drugs also increase. These findings demonstrate the intricate role of various pathophysiological conditions in influencing the drug absorption process, highlighting the importance of these factors in therapeutic strategies.