Which statement about enterohepatic cycling is true?

• A. It cannot be detected by plasma monitoring alone.
• B. It can create secondary peaks and diurnal patterns in plasma concentration.
• C. It always increases clearance.
• D. It is unaffected by concomitant medications.

Answer: (B)

Enterohepatic cycling happens when a drug that is excreted into bile into the gut can be reabsorbed back into the bloodstream. After biliary excretion, the drug can be deconjugated or unmodified by gut processes and then taken up again by the portal circulation. This re-entry into systemic circulation often shows up as a second rise in plasma concentration after the initial peak. Because bile flow and intestinal transit are influenced by meals and the body's daily rhythms, the reabsorption can cause diurnal (time-of-day) patterns in plasma levels. Those features—secondary peaks and diurnal fluctuations—are the hallmark that makes this statement true.

Plasma concentration monitoring can reveal enterohepatic cycling through observed secondary peaks or a longer-than-expected tail in the concentration-time profile, even if bile sampling isn’t done. In contrast, this cycling does not universally increase clearance; it can prolong apparent exposure (and half-life) rather than consistently raising the clearance rate. And it can be affected by other drugs that alter bile flow, gut flora, or transport processes, so concomitant medications often influence the extent of cycling.