What are the principles of drug absorption in pharmacology?

Principles of Drug Absorption in Pharmacology

Drug absorption is primarily governed by passive diffusion across biological membranes, with most drugs achieving full absorption despite age-related physiological changes that may delay the absorption process. 1

Fundamental Mechanisms of Drug Absorption

Routes of Administration and Absorption

• Oral administration: Most commonly used route where drugs are absorbed primarily from the small intestine 2
• Passive diffusion: Primary mechanism for most drugs, driven by concentration gradient across membranes 1
• Active transport: Some drugs require specific transporters (e.g., P-glycoprotein) that can be affected by inhibitors or inducers 1
• First-pass metabolism: Drugs absorbed from GI tract pass through liver before reaching systemic circulation, potentially reducing bioavailability 1

Factors Affecting Drug Absorption

Physiochemical Properties of Drugs

• Lipophilicity: Highly lipophilic drugs (log P >0) penetrate cell membranes more readily than hydrophilic drugs 1
• Ionization state: Depends on drug pKa and environmental pH; non-ionized forms are better absorbed 3
• Molecular size: Smaller molecules generally have better absorption 3
• Solubility: Drugs must dissolve before absorption; poor solubility limits absorption 4

Physiological Factors

• Gastrointestinal pH: Affects drug ionization and dissolution; reduced gastric acid can impact absorption of drugs requiring acidic environment 1
• Gastric emptying rate: Delayed emptying can slow absorption; faster emptying may reduce absorption time 1
• Intestinal transit time: Affects duration of exposure to absorption sites 2
• Splanchnic blood flow: Reduced flow decreases absorption rate 1
• Intestinal surface area: Greater surface area in proximal small intestine makes it the primary absorption site for most drugs 2

Age-Related Changes Affecting Drug Absorption

• Reduced gastric acid production: Can decrease absorption of drugs requiring acidic environment 1
• Decreased gastric emptying: Delays absorption but typically doesn't affect total amount absorbed 1
• Reduced splanchnic blood flow: May slow absorption rate 1
• Decreased gut wall transporters: Can alter bioavailability of certain drugs 1
• Reduced first-pass metabolism: Can increase bioavailability of drugs like diltiazem, propranolol, and verapamil 1

Food Effects on Drug Absorption

• Delayed gastric emptying: Food generally slows gastric emptying, potentially delaying absorption 5
• Increased bioavailability: Some drugs show increased absorption when taken with food (e.g., metformin) 5
• Binding interactions: Certain foods may bind to drugs, reducing absorption 6
• pH effects: Food can alter gastric pH, affecting drug dissolution 7
• Formulation considerations: Enteric-coated tablets may be retained in stomach during digestive period, delaying absorption 7

Special Considerations for Different Drug Classes

Stimulant Medications

• Rapidly absorbed from gut, acting within 30 minutes of ingestion 1
• Absorption rate affects clinical response; immediate-release formulations create rapid plasma concentration peaks 1
• Modern formulations can achieve equivalent therapeutic effects with gradual absorption profiles 1

Cardiovascular Drugs

• Lipophilic drugs (amiodarone, propranolol) have increased volume of distribution in older adults 1
• Hydrophilic drugs (digoxin, ACEIs) may reach higher peak concentrations in elderly patients 1
• Sex differences exist in pharmacokinetics, with women often showing higher bioavailability of CYP3A4 substrates 1

Clinical Applications and Pitfalls

Common Pitfalls in Drug Absorption

• Assuming consistent absorption across patient populations: Age, sex, and disease states significantly alter absorption parameters 1
• Overlooking food-drug interactions: Meal timing can substantially affect absorption of certain medications 5, 7
• Ignoring formulation differences: Generic and brand-name products may have different absorption profiles 1
• Failing to consider drug-drug interactions: Concomitant medications may alter gut transporters or metabolism 1

Strategies to Optimize Drug Absorption

• Timing administration relative to meals: Consider whether drugs should be taken with or without food 5
• Selecting appropriate formulations: Choose immediate or extended-release based on therapeutic goals 1
• Monitoring therapeutic drug levels: Consider therapeutic drug monitoring for drugs with narrow therapeutic windows 1
• Adjusting for patient factors: Consider age, sex, and comorbidities when predicting absorption 1

By understanding these principles of drug absorption, clinicians can better predict drug behavior, optimize dosing regimens, and minimize adverse effects while maximizing therapeutic benefits.