Pharmacokinetics and Bioavailability

Bioavailability

Definition

Bioavailability refers to the fraction of an administered dose of a drug that reaches the systemic circulation in an unchanged form and is available for therapeutic action. It is typically expressed as a percentage. For drugs administered intravenously, bioavailability is 100%, as they enter the bloodstream directly. For other routes (e.g., oral), bioavailability is often less than 100% due to factors like absorption, first-pass metabolism, and drug formulation.

Importance

Bioavailability is crucial for determining the appropriate dosage of a drug. A drug with low bioavailability may require a higher dose or alternative route of administration to achieve therapeutic levels in the bloodstream.

Factors Affecting Bioavailability

• Route of Administration:
  • Intravenous (IV): 100% bioavailability, as the drug directly enters the bloodstream.
  • Oral: Often has lower bioavailability due to barriers like absorption through the gastrointestinal (GI) tract and first-pass metabolism in the liver.
  • Other Routes (e.g., sublingual, inhalation): Can offer higher bioavailability than oral routes due to avoidance of the first-pass effect.
• Drug Formulation:
  • Solubility: Drugs must dissolve in the GI fluids for absorption; highly water-soluble drugs may have better bioavailability.
  • Particle Size: Smaller particles dissolve more readily, leading to better absorption.
  • pH Stability: Drugs must be stable in the stomach’s acidic environment and intestinal pH for optimal absorption.
• First-Pass Metabolism: Drugs taken orally first pass through the liver before reaching systemic circulation, where enzymes may metabolize a portion of the drug, reducing bioavailability.
• GI Tract Factors:
  • GI Motility: Faster gastric emptying (e.g., with certain liquids) may increase absorption; delayed emptying can slow absorption.
  • Surface Area for Absorption: Most drug absorption occurs in the small intestine, which has a large surface area due to villi and microvilli.
  • Presence of Food: Food can either enhance or hinder drug absorption.
• pH and Ionization: Drugs can exist in ionized or non-ionized forms depending on the pH of the environment. Non-ionized forms cross cell membranes more easily.
• Drug Transporters and Efflux Pumps: P-glycoprotein (P-gp) in the intestinal wall pumps some drugs back into the GI lumen, reducing absorption. Drugs that are P-gp substrates, such as digoxin, may have reduced bioavailability.
• Physiological Factors: Factors such as age, health conditions, and concurrent medications can impact bioavailability.
• Interactions with Other Drugs: Some drugs may inhibit or induce enzymes responsible for metabolism, affecting the bioavailability of other drugs.

Clinical Implications of Bioavailability

Understanding bioavailability is essential for dosing accuracy and therapeutic effectiveness. Drugs with low bioavailability may require adjustments in dosing or alternative routes to reach therapeutic levels. Additionally, factors affecting bioavailability should be considered in drug development and when tailoring treatments to individual patients.