Bioavailability

Definition

Bioavailability is a measurement of the rate and extent of a therapeutically active drug that reaches the systemic circulation and is available at the site of action.^[1] It is denoted by the letter F.

Absolute bioavailability

Absolute bioavailability compares the bioavailability (estimated as the area under the curve, or AUC) of the active drug in systemic circulation following non-intravenous administration (i.e., after oral, rectal, transdermal, subcutaneous, or sublingual administration), with the bioavailability of the same drug following intravenous administration. It is the fraction of the drug absorbed through non-intravenous administration compared with the corresponding intravenous administration of the same drug. The comparison must be dose normalized if different doses are used; consequently, each AUC is corrected by dividing the corresponding dose administered.

In order to determine absolute bioavailability of a drug, a pharmacokinetic study must be done to obtain a plasma drug concentration vs timeplot for the drug after both intravenous (IV) and non-intravenous administration. The absolute bioavailability is the dose-corrected area under curve (AUC) non-intravenous divided by AUC intravenous. For example, the formula for calculating F for a drug administered by the oral route (po) is given below.

Relative bioavailability

This measures the bioavailability (estimated as area under the curve, or AUC) of a certain drug when compared with another formulation of the same drug, usually an established standard, or through administration via a different route. When the standard consists of intravenously administered drug, this is known as relative bioavailability.

Factors influencing bioavailability

The absolute bioavailability of a drug, when administered by an extravascular route, is usually less than one (i.e. F<1).>

Such factors may include, but are not limited to:

• Physical properties of the drug (hydrophobicity, pKa, solubility)
• The drug formulation (immediate release, excipients used, manufacturing methods, modified release - delayed release, extended release, sustained release, etc.)
• If the drug is administered in a fed or fasted state
• Gastric emptying rate
• Circadian differences
• Enzyme induction/inhibition by other drugs/foods:
  • Interactions with other drugs (e.g. antacids, alcohol, nicotine)
  • Interactions with other foods (e.g. grapefruit juice, pomello, cranberry juice)
• Transporters: Substrate of an efflux transporter? (e.g. P-glycoprotein)
• Health of the GI tract
• Enzyme induction/inhibition by other drugs/foods:
  • Enzyme induction (increase rate of metabolism). e.g. Phenytoin (antiepileptic) induces CYP1A2, CYP2C9, CYP2C19 and CYP3A4
  • Enzyme inhibition (decrease rate of metabolism). e.g. grapefruit juice inhibits CYP3A --> higher nifedipine concentrations
• Individual Variation in Metabolic Differences
  • Age: In general, drugs metabolized more slowly in fetal, neonatal, and geriatric populations
  • Phenotypic differences, enterohepatic circulation, diet, gender.
• Disease state