Why are drugs with extensive first-pass metabolism sometimes given orally?

Why are drugs with extensive first-pass metabolism sometimes given orally?

• A. Because first-pass metabolism does not affect bioavailability.
• B. Because the oral dose must be increased to achieve systemic effect.
• C. Because first-pass metabolism is irrelevant for these drugs.
• D. Because they are not absorbed from the gut.

Answer: (B)

First-pass metabolism in the gut wall and liver can dramatically reduce the amount of drug that reaches the systemic circulation when a drug is taken by mouth. To achieve the same therapeutic level in the blood as with other routes, the oral dose is often increased to compensate for this loss. In other words, more drug is given orally so that enough unchanged drug survives first-pass metabolism to produce the desired systemic effect. This approach works because the goal is to overcome the reduction in bioavailability caused by hepatic and intestinal enzymes. Keep in mind that this strategy can introduce more variability between individuals due to differences in metabolism, so alternative routes that bypass first-pass or formulation strategies are sometimes preferred.

First-pass metabolism in the gut wall and liver can dramatically reduce the amount of drug that reaches the systemic circulation when a drug is taken by mouth. To achieve the same therapeutic level in the blood as with other routes, the oral dose is often increased to compensate for this loss. In other words, more drug is given orally so that enough unchanged drug survives first-pass metabolism to produce the desired systemic effect. This approach works because the goal is to overcome the reduction in bioavailability caused by hepatic and intestinal enzymes. Keep in mind that this strategy can introduce more variability between individuals due to differences in metabolism, so alternative routes that bypass first-pass or formulation strategies are sometimes preferred.