Pharmacokinetics: Drug Absorption

Pharmacokinetics: drug absorption explores how medications move from their administration site into the bloodstream and reach target tissues. This comprehensive study examines drug transport mechanisms, dissolution processes, and factors affecting bioavailability across various delivery routes. JoVE Coach provides essential foundation knowledge for understanding pharmaceutical sciences and therapeutic effectiveness.

• Understand the four phases of drug therapy: pharmaceutic, pharmacokinetic, pharmacodynamic, and therapeutic
• Identify major drug delivery routes including enteral, parenteral, and topical administration methods
• Analyze cellular membrane structure and drug transport mechanisms across biological barriers
• Explore passive diffusion, active transport, and carrier-mediated drug movement processes
• Learn factors influencing drug absorption including anatomical, physiological, and pharmaceutical parameters
• Apply dissolution theories and understand particle size effects on drug bioavailability
• Examine presystemic elimination and first-pass metabolism impact on drug effectiveness
• Evaluate methods for studying drug absorption through in vitro and in situ techniques

1. Drug Administration Routes and Bioavailability: Oral medications like aspirin tablets must dissolve in gastrointestinal fluids before absorption, while intravenous drugs like morphine enter circulation directly with 100% bioavailability. Sublingual nitroglycerin bypasses liver metabolism for rapid angina relief, demonstrating how route selection impacts therapeutic outcomes. Understanding bioavailability differences helps explain why oral morphine requires higher doses than intravenous administration to achieve equivalent pain relief.

2. Cellular Membrane Transport Mechanisms: Drug molecules cross cell membranes through passive diffusion, active transport, or carrier-mediated processes. Lipophilic drugs like propranolol easily diffuse through membrane lipid bilayers, while hydrophilic drugs like furosemide require specific transporters. The blood-brain barrier's tight junctions limit drug penetration, explaining why only certain antibiotics like linezolid effectively treat brain infections while others remain ineffective despite adequate blood levels.

3. Dissolution and Drug Release: Solid dosage forms must disintegrate and dissolve before absorption occurs. Poorly soluble drugs like griseofulvin benefit from micronization to increase surface area and dissolution rates. Extended-release formulations like metformin XR use special coatings to control drug release over 12-24 hours, reducing dosing frequency while maintaining therapeutic levels throughout the day.

4. First-Pass Metabolism and Presystemic Elimination: Oral drugs absorbed from the intestine pass through the liver before reaching systemic circulation, where hepatic enzymes may metabolize significant amounts. Drugs with high first-pass metabolism like nitroglycerin lose 90% of their dose during liver passage, necessitating alternative routes or higher oral doses. This explains why sublingual nitroglycerin provides effective angina treatment while oral formulations prove inadequate.

5. Factors Affecting Drug Absorption: Gastrointestinal pH variations influence weak acid and base absorption, with aspirin (weak acid) favoring stomach absorption while quinidine (weak base) absorbs better in alkaline intestinal conditions. Food interactions can enhance or impair absorption - fatty meals increase griseofulvin absorption but delay acetaminophen absorption. Disease states like celiac disease reduce intestinal surface area, significantly impairing drug absorption for multiple medications.

6. Pharmaceutical Formulation Impact: Excipients and manufacturing processes significantly influence drug dissolution and absorption. Enteric-coated omeprazole protects acid-sensitive drugs from stomach degradation, while immediate-release formulations provide rapid onset. Surfactants in formulations improve wetting of hydrophobic drugs, while disintegrants promote tablet breakup. Understanding these relationships explains bioequivalence requirements for generic medications and therapeutic failures with poorly formulated products.