What factors modify drug absorption?

Factors Modifying Drug Absorption

Drug absorption is influenced by multiple physiological, pathological, and environmental factors that can significantly impact drug bioavailability and therapeutic efficacy. Understanding these factors is essential for optimizing drug therapy and minimizing adverse effects.

Physiological Factors

Gastrointestinal Factors

• pH of GI tract: Affects ionization and dissolution of drugs
• GI motility: Faster transit time reduces absorption time
• Surface area available for absorption: Determines absorption capacity
• Splanchnic blood flow: Affects rate of drug delivery to systemic circulation
• Gut wall transporters: P-glycoprotein and other transporters can affect drug uptake
• Gut wall metabolizing enzymes: Contribute to first-pass metabolism 1

Patient-Specific Factors

• Age: Significantly affects pharmacokinetics through:
  • Reduced gastric acid production and emptying in elderly
  • Decreased splanchnic blood flow
  • Reduced GI motility
  • Changes in body composition 1
• Body weight/BMI: Obesity can modify drug pharmacokinetics:
  • Accelerated gastrointestinal transit
  • Shortened gastric emptying
  • Reduced lean-to-fat ratio affecting volume of distribution
  • Altered liver biotransformation 2

Environmental Factors

Food Effects

• Fed vs. fasting state: Food can significantly alter drug absorption
  • Example: Rivaroxaban absorption increases by 28-41% when taken with food
  • Food delays time to peak plasma concentration (from 2.75h to 4.0h for rivaroxaban)
  • Food can reduce interindividual variability in absorption 2
• Meal composition: High-fat meals may increase absorption of lipophilic drugs, though some drugs (like rivaroxaban) show no difference between high-fat and high-carbohydrate meals 2

Route of Administration

• Oral vs. intravenous: Oral administration is preferred when feasible and absorption can be reasonably warranted
• Intramuscular route: Should be avoided in postoperative pain management
• Epidural/regional administration: Recommended when feasible in emergency surgery situations 2

Drug-Drug Interactions

Pharmacokinetic Interactions

• Gastric pH modifiers:
  • Drugs that alter gastric pH (H2 antagonists, antacids) may affect absorption of pH-dependent drugs
  • Example: Pantoprazole reduces dabigatran etexilate absorption by 32-40% 2
• P-glycoprotein inhibitors/inducers: Affect bioavailability of drugs that are P-gp substrates 2
• NSAIDs and anticoagulants:
  • Naproxen increases rivaroxaban plasma concentration by approximately 10%
  • Combined use of rivaroxaban and naproxen significantly increases bleeding time 2

Physical/Chemical Interactions

• Adsorption: Some drugs may bind to other drugs in the GI tract
• Chelation: Formation of non-absorbable complexes
• Direct chemical interactions in the GI tract 3

Pathological Conditions

Gastrointestinal Disease

• Altered GI transit time: Affects drug delivery to absorption sites
• Changes in pH: Affects drug dissolution and ionization
• Reduced absorptive surface area: In conditions like Crohn's disease
• Postoperative ileus: Inevitable consequence of abdominal surgery that affects drug absorption 2

Clinical Implications and Recommendations

1. Consider food effects when prescribing medications:

   • Some drugs should be taken with food to enhance absorption (e.g., rivaroxaban)
   • Others may require administration on an empty stomach

2. Adjust dosing in patients with extreme body weights:

   • For hydrophilic drugs like LMWH, body weight-adjusted dosing may result in overdosing in severely obese individuals 2
   • Consider drug's lipophilic characteristics when dosing in obese patients

3. Account for drug-drug interactions:

   • Avoid or monitor closely when combining drugs that affect bleeding risk (e.g., rivaroxaban with NSAIDs or aspirin)
   • Consider the impact of acid-suppressing medications on drug absorption

4. Select appropriate administration routes:

   • Oral administration is preferred when feasible
   • Avoid intramuscular route for postoperative pain management
   • Consider epidural/regional anesthesia when appropriate 2

5. Monitor drug effects more closely in patients with GI disease:

   • Unpredictable absorption patterns may necessitate therapeutic drug monitoring
   • Consider alternative routes of administration when GI absorption is compromised

Understanding these factors that modify drug absorption is crucial for optimizing therapeutic outcomes and minimizing adverse effects in clinical practice.