What feature in a plasma concentration–time profile would most strongly indicate enterohepatic cycling?

• A. A monophasic decline after Cmax.
• B. Multiple peaks in the profile, including secondary peaks.
• C. A rapid initial peak followed by a linear decline with no fluctuations.
• D. A completely flat profile after administration.

Answer: (B)

Enterohepatic cycling creates a reentry of the drug into the bloodstream after it’s excreted into bile and released back in the gut. This reabsorption can produce additional bursts of systemic drug, leading to secondary peaks in the plasma concentration–time profile. The presence of multiple peaks, including secondary peaks, is a strong signature of this recycling process, and their timing depends on GI transit and bile release. In contrast, a monophasic decline after the initial peak reflects simple first-order elimination with no reabsorption; a rapid initial peak followed by a smooth linear decline suggests one absorption-and-elimination phase without fluctuations; and a completely flat profile implies little to no systemic exposure. So the multiple-peak pattern best indicates enterohepatic cycling.