Enzymes in the liver, part of the cytochrome P450 family, are responsible for the breakdown/oxidation of various products in the body. These enzymes can be induced or inhibited (up-regulated or down-regulated). This is really important for some drugs that have a narrow therapeutic window (ie the difference between a drug having a therapeutic effect and overdose).
For example, if a patient is on warfarin then they have their clotting factors titrated to a specific value. Other drugs and dietary factors which effect the CYP450 system can shift this value and cause perfuse bleeding or bad clotting; like a stroke. Grapefruit is the classic example as it is a CYP450 inhibitor and therefore can increase your clotting value and make you prone to bleeding. So patients who are warfrinised are told to avoid grapefruit.
But, of course there are other drugs it can effect as it is a general CYP450 inhibitor. For most drugs that do not have a narrow window of use this is irrelevant. For others it can be important.
Other drugs include phenytoin for epilepsy, amiodarone for heart arrythmias and even the oral contraceptive (effected more by inducers than inhibitors).
Also, other foods have this effect, it's just grapefruit is the most common example and the classic example.
Hepatic first-pass metabolism, as you clearly know, is another major factor in effective bioavailability of a drug (or vitamin). Obviously drugs given IV, intramuscular or even PR (rectally) avoid first-pass metabolism as they get to the main circulation without going via the liver. However, vitamins and supplements are usually more effected by the kidneys than the liver. A lot of these 'high' dose supplements are pointless as the kidneys cannot reabsorb them out of the filtrate, so they just get excreted via the urine. If you hammer some vitamins you'll notice your pee change colour, barocca is the classic.
The best way to supplement is small amounts throughout the day to allow your body to utilise it, although again, most supplements are just marketing rubbish anyway.
or come out with stroke face!
