Which statement about first-pass metabolism is true?

Which statement about first-pass metabolism is true?

• A. It increases oral bioavailability of all drugs.
• B. It occurs in the kidneys before systemic distribution.
• C. It has no effect on oral medications.
• D. It reduces the amount of active drug reaching systemic circulation.

Answer: (D)

First-pass metabolism describes the loss of drug that occurs as it travels from the gut through the liver before reaching the systemic circulation. Enzymes in the intestinal wall and in the liver metabolize a portion of the drug during this passage, so only a fraction enters the bloodstream as active drug. This is why oral bioavailability can be much less than 100% for many medications. The main takeaway is that first-pass metabolism reduces the amount of active drug that ultimately reaches systemic circulation, which is why the statement about this process being true is that it reduces systemic exposure after oral dosing. The other statements don’t fit: first-pass metabolism does not increase bioavailability; it typically lowers it. It doesn’t occur in the kidneys before systemic distribution; it happens mainly in the gut wall and liver via hepatic portal circulation. And it does affect oral medications, often significantly, not nothing. For example, some drugs like nitroglycerin are largely inactivated by first-pass metabolism when taken orally, which is why alternative routes (like sublingual) bypass this effect.

First-pass metabolism describes the loss of drug that occurs as it travels from the gut through the liver before reaching the systemic circulation. Enzymes in the intestinal wall and in the liver metabolize a portion of the drug during this passage, so only a fraction enters the bloodstream as active drug. This is why oral bioavailability can be much less than 100% for many medications. The main takeaway is that first-pass metabolism reduces the amount of active drug that ultimately reaches systemic circulation, which is why the statement about this process being true is that it reduces systemic exposure after oral dosing.

The other statements don’t fit: first-pass metabolism does not increase bioavailability; it typically lowers it. It doesn’t occur in the kidneys before systemic distribution; it happens mainly in the gut wall and liver via hepatic portal circulation. And it does affect oral medications, often significantly, not nothing. For example, some drugs like nitroglycerin are largely inactivated by first-pass metabolism when taken orally, which is why alternative routes (like sublingual) bypass this effect.