Metabolism and first-pass effect
If a drug is given orally, it is transported to the general circulation via the liver. Thus drugs which are extensively metabolized will be metabolized in the liver during absorption, never reaching their full concentration in the systemic circulation. This is called first-pass metabolism and determines the fraction of the dose that will reach the systemic circulation. This is the reason the propranolol oral dose is somewhat higher than the IV, the same is true for morphine.
There are also metabolic enzymes located in the gastrointestinal lumen. Thus, metabolism can also occur during absorption in the gut, before the drug even reaches the liver.
Click on the 2nd step for an example...
CYP-metabolism of felodipine
The second illustration shows an example with felodipine, a drug which undergoes almost copmlete metabolism in the GI and liver by CYP3A4. With grapefruit, metabolism by CYP3A4 is reduced, an the bioavailability can go up (in the illustration from 15% to 45%).
See how first pass metabolism effects the oral availability of drugs by clicking here and selecting the first pass metabolism (module 2).