Bioavailability Totally Explained

Everything about Bioavailability totally explained

In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via other routes (such as orally), its bioavailability decreases (due to incomplete absorption and first-pass metabolism). Bioavailability is one of the essential tools in pharmacokinetics, as bioavailability must be considered when calculating dosages for non-intravenous routes of administration.

Definition

Bioavailability is a measurement of the extent of a therapeutically active drug that reaches the systemic circulation and is available at the site of action.
It is expressed as the letter F.

Absolute bioavailability

Absolute bioavailability compares the bioavailability (estimated as area under the curve, or AUC) of the active drug in systemic circulation following non-intravenous administration (for example, after oral, rectal, transdermal, subcutaneous 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 time plot 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.

F = frac

Factors influencing bioavailability

The absolute bioavailability of a drug, when administered by an extravascular route, is usually less than one (for example F<1). Various physiological factors reduce the availability of drugs prior to their entry into the systemic circulation,
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
Circadean differences
Enzyme induction/inhibition by other drugs/foods:
- Interactions with other drugs (for example antacids, alcohol, nicotine)
- Interactions with other foods (for example grapefruit juice, pomello, cranberry juice)
Transporters: Substrate of an efflux transporter? (for example P-glycoprotein)
Health of the GI tract
Enzyme induction/inhibition by other drugs/foods:
- Enzyme induction (increase rate of metabolism). for example Phenytoin (antiepileptic) induces CYP1A2, CYP2C9, CYP2C19 and CYP3A4
- Enzyme inhibition (decrease rate of metabolism). for example 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
- for example hepatic insufficiency, poor renal function

Each of these factors may vary from patient to patient (inter-individual variation), and indeed in the same patient over time (intra-individual variation). Whether a drug is taken with or without food will affect absorption, other drugs taken concurrently may alter absorption and first-pass metabolism, intestinal motility alters the dissolution of the drug and may affect the degree of chemical degradation of the drug by intestinal microflora. Disease states affecting liver metabolism or gastrointestinal function will also have an effect.
Relative bioavailability is extremely sensitive to drug formulation. Relative bioavailability is one of the measures used to assess bioequivalence between two drug products, as it's the Test/Reference ratio of AUC. The maximum concentration of drug in plasma or serum (Cmax) is also usually used to assess bioequivalence.

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