Bioavailability and First Pass Metabolism

The oral bioavailability of a drug is a measure of the extent that the drug is able to enter the systemic circulation following oral administration relative to intravenous administration. Bioavailability is expressed in terms of percentage.

The calculation of bioavailability is shown in the following equation:

F = AUCpo=Dosepo x 100 AUCiv/Doseiv

For an orally administered drug to enter the systemic circulation, the drug must be absorbed through the intestinal wall, enter the portal vein, pass through the liver, and enter the systemic circulation (see Fig. 3.1).

Figure 3.1. Movement and barriers of orally dosed drug from intestinal lumen into the systemic circulation.

As depicted in Fig. 3.1, metabolism can occur during passage through the intestinal wall and liver. Metabolism by the intestine and liver prior to reaching the systemic circulation is referred to as first-pass metabolism. Since bioavailability is a function of both absorption and first-pass metabolism of both the intestine and the liver, it can also be described by the following relationship:

where Fa is the fraction absorbed from the intestine, Fg is the fraction that escapes gut (intestinal) metabolism, and Fh is the fraction that escapes hepatic metabolism/elimination.

An alternative method of representing bioavailability in terms of extraction ratios is as follows:

where Eg is the extraction ratio of the gut, and Eh is the extraction ratio of the liver.

Extraction ratios are described in Sect. 1.4.

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