Which routes bypass hepatic first-pass metabolism and can improve bioavailability for certain drugs?

• A. Intravenous, sublingual, and transdermal.
• B. Oral and subcutaneous.
• C. Inhaled only.
• D. Rectal only.

Answer: (B)

The key idea is routes that deliver the drug directly to systemic circulation, avoiding the liver on the first pass, which can boost bioavailability for drugs that are heavily metabolized by the liver after oral administration. Intravenous delivery goes straight into the bloodstream, bypassing the liver entirely at the outset. Sublingual and transdermal routes also avoid first-pass metabolism because the drug enters systemic circulation through mucous membranes or the skin rather than the gastrointestinal tract. Inhaled delivery similarly enters the bloodstream through the lung's alveolar network, bypassing hepatic processing. Rectal administration can bypass the liver to some extent, but it’s variable and not as reliable as the other bypass routes.

Among the options, the combination that includes only routes known to bypass first-pass metabolism is intravenous, sublingual, and transdermal, making it the best choice. The other options mix in oral administration, which undergoes first-pass metabolism, or describe a route in a way that’s incomplete or less reliable for bypassing hepatic processing.