Which route bypasses hepatic first-pass metabolism, potentially achieving higher bioavailability for certain drugs?

• A. Intravenous administration.
• B. Oral administration with meals.
• C. Subcutaneous administration.
• D. Transdermal administration.

Answer: (A)

The concept being tested is how first-pass metabolism in the liver affects drug bioavailability and which routes bypass it. When a drug is swallowed, it is absorbed from the GI tract into the portal circulation and goes to the liver before reaching systemic circulation, so a portion can be metabolized on the first pass, reducing bioavailability. Injecting the drug directly into the bloodstream avoids this entire process, delivering it straight to systemic circulation with essentially full, immediate availability. This is why the intravenous route yields the highest and most reliable bioavailability for drugs that are heavily metabolized by the liver if given by mouth. Other non-oral routes, like subcutaneous or transdermal, also bypass hepatic first-pass, but their absorption dynamics differ and they don’t always provide the same peak systemic levels as IV administration.