After oral administration of a sustained-release preparation of a choleretic agent, the plasma concentration-time profile of a volunteer shows an early absorption peak followed by a distinct smaller second peak at 6 hours. The most likely explanation for this double-peaked profile is:

• A Flip-flop kinetics in which absorption is slower than elimination
• B Two overlapping absorption phases from different segments of the small intestine
• C Saturation of hepatic metabolism at the first peak concentrations
• D Enterohepatic recirculation of secreted bile and reabsorbed drug from the intestine ✓

Explanation

Drugs that undergo enterohepatic cycling are excreted in bile, stored in the gallbladder, and delivered back to the intestine when bile is released, typically after a meal. Reabsorption then produces a characteristic secondary peak several hours after the initial one, and the cycle effectively prolongs apparent half-life. Flip-flop kinetics flattens and prolongs the whole profile without creating a discrete delayed peak, and saturation metabolism causes disproportionate rises rather than a second hump.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th ed.

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