What is oral bioavailability?

Oral Bioavailability: Definition and Clinical Significance

Oral bioavailability is the percentage of a drug absorbed into the systemic circulation after passing through the gut, liver, or lungs following oral administration. 1 This pharmacokinetic parameter is crucial for determining appropriate dosing regimens and predicting therapeutic effectiveness.

Definition and Mechanism

Oral bioavailability represents the fraction of an orally administered drug that:

• Is absorbed from the gastrointestinal tract
• Survives first-pass metabolism in the liver and gut wall
• Reaches the systemic circulation in unchanged form

The bioavailability of a drug is influenced by several factors:

1. First-pass metabolism: Drugs that undergo significant first-pass metabolism typically have lower bioavailability. Drugs inactivated by first-pass metabolism are preferred during lactation. 1

2. Physicochemical properties:

   • Molecular weight (larger molecules have more difficulty passing into circulation)
   • Lipophilicity/hydrophilicity balance
   • pKa and ionization state at physiological pH

3. Formulation factors:

   • Dissolution rate
   • Particle size
   • Excipients used

Measurement and Expression

Bioavailability is typically expressed as a percentage (0-100%) or a fraction (0-1). It is determined by comparing the area under the plasma concentration-time curve (AUC) after oral administration to that after intravenous administration:

• Absolute bioavailability: Compares oral administration to intravenous administration (considered 100% bioavailable)
• Relative bioavailability: Compares one oral formulation to another oral formulation

Clinical Examples and Significance

Bioavailability varies widely among medications:

• High bioavailability drugs (>90%):

  • Fluconazole: ~90% bioavailability 1
  • Voriconazole: >90% bioavailability (not affected by gastric pH but decreases when administered with food) 1

• Moderate bioavailability drugs:

  • Metoprolol: ~50% bioavailability due to pre-systemic metabolism 2
  • Dabigatran etexilate: 6-7% bioavailability in healthy older subjects 1

• Low bioavailability drugs:

  • Rivaroxaban: ~80% bioavailability 1
  • Apixaban: 45% bioavailability 1

Clinical Implications

Understanding oral bioavailability has important clinical implications:

1. Dosing considerations: Drugs with low bioavailability often require higher oral doses to achieve therapeutic plasma concentrations

2. Formulation selection: For drugs with poor bioavailability, specialized formulations may be necessary:

   • Dabigatran etexilate is formulated as capsules containing pellets with tartaric acid cores to create an acidic microenvironment that improves dissolution and absorption 1
   • Itraconazole absorption is improved when taken with food or acidic beverages 1

3. Route of administration decisions: When oral bioavailability is very poor, parenteral administration may be preferred:

   • Parenteral antibiotics achieve therapeutic serum levels faster and more reliably than oral formulations 1
   • Some drugs (insulin, heparin) have poor oral bioavailability and are only available as injectable formulations 1

Special Populations

Bioavailability can be affected by patient-specific factors:

• Hepatic impairment: May increase bioavailability of drugs that undergo extensive first-pass metabolism
• Genetic variations: CYP2D6 polymorphisms affect metoprolol metabolism, with poor metabolizers having higher plasma concentrations 2
• Age-related changes: Geriatric patients may show slightly higher plasma concentrations of some drugs due to decreased metabolism and hepatic blood flow 2

Practical Considerations

When prescribing medications:

• Consider bioavailability when switching between oral and intravenous formulations
• Be aware of food effects on absorption (e.g., voriconazole absorption decreases with food, while itraconazole capsule absorption increases with food) 1
• For drugs with poor bioavailability, consider timing of administration relative to meals
• Monitor for drug interactions that may affect bioavailability through changes in metabolism or absorption

Understanding oral bioavailability is essential for optimizing drug therapy and ensuring that patients receive appropriate doses to achieve therapeutic effects while minimizing adverse reactions.