Which method of medication administration is associated with the greatest first-pass effect?

The method of medication administration that is associated with the greatest first-pass effect is oral administration. This phenomenon occurs because medications taken by mouth must pass through the gastrointestinal tract and then through the liver before they enter systemic circulation. During this process, a significant portion of the drug may be metabolized, thus reducing the amount of active drug that reaches the bloodstream.

In contrast, methods such as sublingual, intravenous, and subcutaneous do not involve this extensive metabolic pathway. Sublingual administration bypasses the gastrointestinal tract entirely, leading to direct absorption into the bloodstream. Intravenous administration delivers medication directly into circulation, avoiding any first-pass metabolism, while subcutaneous administration also allows for more direct entry into the body without passing through the liver before reaching systemic circulation. Therefore, oral administration has the highest first-pass effect, making it crucial for healthcare professionals to consider this factor when dosing medications taken by mouth.