Drug Absorption and Bioavailability

Patient-Related Factors

• Obesity can modify drug pharmacokinetics by accelerating gastrointestinal transit, shortening gastric emptying, reducing lean-to-fat ratio affecting volume of distribution, and altering liver biotransformation, according to the European Society of Cardiology 1
• Body weight and BMI significantly affect pharmacokinetics, with hydrophilic drugs like LMWH potentially resulting in overdosing in severely obese individuals, as recommended by the European Society of Cardiology 1
• Age significantly affects pharmacokinetics through reduced gastric acid production and emptying, decreased splanchnic blood flow, and reduced GI motility, as well as through multiple mechanisms including changes in body composition, reduced hepatic blood flow, decreased plasma albumin levels, and reduced renal function 2, 3

Food and Drug Interactions

• Food can significantly alter drug absorption, with rivaroxaban absorption increasing by 28-41% when taken with food, and food delaying time to peak plasma concentration, as reported by the American College of Chest Physicians 4
• Meal composition, such as high-fat meals, may increase absorption of lipophilic drugs, although some drugs like rivaroxaban show no difference between high-fat and high-carbohydrate meals, according to the American College of Chest Physicians 4
• Gastric pH modifiers, such as H2 antagonists and antacids, may affect absorption of pH-dependent drugs, with pantoprazole reducing dabigatran etexilate absorption by 32-40%, as reported by the American College of Chest Physicians 4

Drug-Drug Interactions

• P-glycoprotein inhibitors/inducers can affect bioavailability of drugs that are P-gp substrates, as reported by the American College of Chest Physicians 4
• NSAIDs and anticoagulants, such as naproxen and rivaroxaban, can increase bleeding time when used in combination, according to the American College of Chest Physicians 4

Administration Routes

• Oral administration is preferred when feasible, although intramuscular route should be avoided in postoperative pain management, and epidural/regional administration is recommended when feasible in emergency surgery situations, as suggested by the World Society of Emergency Surgery 5
• Epidural/regional anesthesia is recommended when appropriate, particularly in emergency surgery situations, according to the World Society of Emergency Surgery 5

Clinical Considerations

• Postoperative ileus can affect drug absorption, and altered GI transit time can impact drug delivery to absorption sites, as reported by the World Society of Emergency Surgery 5
• Changes in pH can affect drug dissolution and ionization, and reduced absorptive surface area can impact drug absorption in conditions like Crohn's disease
• Gastrointestinal factors, including surface area available for absorption, activity of gut wall transporters, first-pass metabolism capability, presence of metabolizing enzymes, and mucosal barrier function, are critical for drug absorption [2, 3]
• Hepatic and splanchnic blood flow significantly impact drug absorption and distribution, affecting clearance of drugs with high extraction ratios, rate of drug delivery to the liver, tissue perfusion, and drug distribution [2, 1]
• Therapeutic drug monitoring may be necessary in patients with unpredictable absorption patterns, and alternative routes of administration should be considered when GI absorption is compromised, as recommended by the European Society of Cardiology 1
• Clinicians should focus on age-related physiological changes, gastrointestinal disease states, hepatic and renal function, and drug interactions affecting metabolizing enzymes and transporters to optimize drug therapy and minimize adverse effects [2]
• The position of the patient when the drug is taken does not significantly affect an orally-administered drug's absorption and/or distribution in the body, as patient position may have minor effects on gastric emptying rates, but is not a major determinant of drug absorption compared to other factors [2, 3]