Oral bioavailability

The fraction of an orally-administered dose of drug that reaches the systemic circulation and, as with bioavailability, abbreviated as F. Following oral administration, the drug must be absorbed across the walls of the GI tract and then must escape metabolism as it passes through the liver, in order to reach the systemic circulation. The oral bioavailability is equal to the product of the fraction of the dose that is absorbed from the gut (f_g) and the fraction of that absorbed portion that then escapes from the liver (f_H). So F = f_g × f_H.

The hepatic extraction ratio refers to the fraction of drug removed from the blood on a single pass through the liver, a value which is equal to 1-f_H. A drug can not generally have an oral bioavailability value higher than its value for f_H, and oral bioavailability can equal f_H only when all of the drug escapes from the GI tract and is able to enter the portal circulation (i.e. when f_g = 1). However, some orally-administered drugs are able to avoid first-pass metabolism, to some degree at least, as a result of lymphatic drug absorption. Oral bioavailability would then be higher than predicted, based on consideration of hepatic extraction ratio and f_H.

Neither f_g nor f_H can be measured directly; instead, F is determined by comparing area under the curve of a plasma concentration versus time plot for an orally-administered dose with the area under the curve following an IV dose of the same amount of the same drug to the same patient. The ratio of areas (AUC_PO/AUC_IV) reveals oral bioavailability, since AUC is proportional to the amount of drug that was present within the systemic circulation.

Further comments pertinent to oral bioavailability are included under the entry for bioavailability. Click here to view a short vodcast explaining oral bioavailability.