What happens to an oral drug before it reaches the bloodstream
After a tablet dissolves, the drug is absorbed across the gut wall into the portal vein, which carries it straight to the liver before any of it reaches the general circulation. Both the intestinal wall and the liver contain metabolising enzymes, so a fraction of the dose can be chemically altered or inactivated on this first pass. What survives this gauntlet and reaches systemic circulation defines the drug's oral bioavailability.
For some drugs this loss is modest; for others it is severe enough that the oral dose must be many times the intravenous dose to achieve the same effect, and a few drugs are so heavily extracted that oral use is impractical.
Why route of administration changes the dose
Routes that bypass the portal circulation, such as intravenous, sublingual, buccal, or transdermal delivery, avoid much of the first-pass loss because the drug enters the bloodstream before reaching the liver. This is why glyceryl trinitrate is given sublingually rather than swallowed and why some hormones are delivered transdermally.
First-pass metabolism varies between people because of genetic and liver-function differences, so equivalent oral doses do not always produce equivalent blood levels. This is general educational information, not medical advice; route and dose decisions should be made by a qualified clinician.