Which of the following offers the most likely explanation for the substantially higher peak plasma concentration of acetaminophen following IV administration when compared to oral and rectal routes?Question 32 Answer Choices A. The drug is poorly absorbed through mucous membranes in the oral cavity and rectum. B. A substantial portion of the drug is excreted in the feces before it can be absorbed. C. Much of the drug is broken down in the digestive tract prior to absorption. D. The liver breaks down a large portion of the drug before it reaches the systemic circulation after oral or rectal administration.
Question
Which of the following offers the most likely explanation for the substantially higher peak plasma concentration of acetaminophen following IV administration when compared to oral and rectal routes?Question 32 Answer Choices A. The drug is poorly absorbed through mucous membranes in the oral cavity and rectum. B. A substantial portion of the drug is excreted in the feces before it can be absorbed. C. Much of the drug is broken down in the digestive tract prior to absorption. D. The liver breaks down a large portion of the drug before it reaches the systemic circulation after oral or rectal administration.
Solution
The most likely explanation for the substantially higher peak plasma concentration of acetaminophen following IV administration when compared to oral and rectal routes is D. The liver breaks down a large portion of the drug before it reaches the systemic circulation after oral or rectal administration.
This is due to a phenomenon known as the first-pass effect or first-pass metabolism. When a drug is taken orally or rectally, it is absorbed from the digestive tract and enters the hepatic portal system. It is carried through the portal vein into the liver before it reaches the rest of the body. The liver metabolizes many drugs, sometimes to such an extent that only a small amount of active drug emerges from the liver to the rest of the circulatory system. This first pass through the liver thus may greatly reduce the bioavailability of the drug.
In contrast, when a drug is administered intravenously, it is distributed directly into the systemic circulation without first passing through the liver, leading to higher plasma concentrations.
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