You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information.
What is The most impoant factor decreasing the systemic bioavailability of orally administered drugs is and explain in detail?
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