Which route of administration does not completely bypass the liver?

Rectal administration is unique among the various routes of administration because it can partially bypass the liver's first-pass metabolism. When a drug is administered rectally, it is absorbed by the rectal mucosa and enters the systemic circulation through the inferior rectal vein, which drains directly into the systemic circulation. However, the upper part of the rectum drains through the superior rectal vein into the portal circulation, sending some of the drug to the liver before it reaches the systemic circulation.

This means that while rectal administration does not completely circumvent the liver, it mitigates the extent of first-pass metabolism compared to oral administration, where all absorbed substances must pass through the liver first.

Intravenous administration completely bypasses the liver because the drug is injected directly into the bloodstream. Oral administration, on the other hand, involves absorption in the gastrointestinal tract and goes directly to the liver via the portal vein, making it subject to significant first-pass metabolism. Subcutaneous administration typically allows for drug absorption into the systemic circulation without significant first-pass effect, similar to intravenous routes.

Thus, rectal administration is the correct choice as it allows for some absorption to directly enter systemic circulation while still allowing some portion of the drug to be metabolized by the liver.