A researcher is working to develop a newly developed synthetic opioid that has twice the analgesic capability of morphine. After oral ingestion of a fixed dose by several volunteers, the plasma concentration of the drug is measured and determined to be subtherapeutic. Rectal administration of the same dose of the drug shows a plasma concentration well within the therapeutic range, almost double the level measured after oral intake. Which of the following best accounts for the observed difference in drug concentration following rectal administration when compared to oral administration?

Question

A researcher is working to develop a newly developed synthetic opioid that has twice the analgesic capability of morphine.  After oral ingestion of a fixed dose by several volunteers, the plasma concentration of the drug is measured and determined to be subtherapeutic.  Rectal administration of the same dose of the drug shows a plasma concentration well within the therapeutic range, almost double the level measured after oral intake.  Which of the following best accounts for the observed difference in drug concentration following rectal administration when compared to oral administration?

Quizplus · Accepted Answer

Eductional Objective: Bioavailability is the fraction of an administered drug that reaches the systemic circulation unchanged.  Drugs administered orally enter the portal circulation and are subject to first-pass metabolism.  Rectal administration is capable of partially bypassing first-pass metabolism as a proportion of rectal blood flow enters the systemic circulation directly.  Drugs that undergo extensive first-pass metabolism have increased bioavailability when administered rectally.

A Researcher Is Working to Develop a Newly Developed Synthetic