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Bioavailability

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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. Bioavailability is also described as a measurement of the extent of a therapeutically active drug that reaches the systemic circulation and is available at the site of action. 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.

• Absolute bioavailability measures the availability of the active drug in systemic circulation after non-intravenous administration (i.e., after oral, rectal, transdermal, subcutaneous administration). In order to determine absolute bioavailability of a drug (or any measured agent), a pharmacokinetic study must be done to obtain a plasma drug concentration versus time plot for the drug after both intravenous (IV) and non-intravenous administration. The absolute bioavailability (F) is the dose-corrected area under the curve (AUC) non-intravenous divided by the AUC intravenous. For example, the formula for calculating F for a drug administered by the oral route (po) is:
  
  F = [AUC]_po * dose_iv / [AUC]_iv * dose_po

Therefore, a drug given by the intravenous route will have an absolute bioavailability of 1 (F=1) while drugs given by other routes usually have an absolute bioavailability of less than one.

• Relative bioavailability measures the bioavailability 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 absolute bioavailability.

Relative bioavailability = [AUC]_A * dose_B / [AUC]_B * dose_A

The absolute bioavailability of a drug, when administered by an extravascular route, is usually less than one (i.e. 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: poor absorption from the gastrointestinal tract; degradation or metabolism of the drug prior to absorption; and hepatic first pass effect. Each of these factors may vary from patient to patient, and indeed in the same patient over time. 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.

Walker Downey & Associates applies its expert Statistical Services to help clients evaluate data collected for product bioavailability determinations.