The most impoant factor decreasing the systemic bioavailability of orally administered drugs is

Bioavailability is defined as the fraction of unchanged drug reaching the systemic circulation following administration by any route. For an intravenous dose of the drug, bioavailability is assumed to be equal to unity. For a drug administered orally, bioavailability may be less than 100% for two main reasons: 1. The incomplete extent of absorption across the gut wall and 2. First-pass elimination by the liver 1st pass elimination is also called pre-systemic elimination Reference: Katzung Pharmacology; 13th edition; Chapter 3; Pharmacokinetics & Pharmacodynamics: Rational Dosing & the Time Course of Drug Action