A pharmaceutical company in the final stages of designing a new nonsteroidal anti-inflammatory agent develops 2 different oral formulations of the drug. Two groups of volunteers are each administered a different formulation, and average plasma drug levels are monitored over the next 12 hours. The results are shown below: Compared to the red curve, the formulation represented by the blue curve is most likely to have which of the following characteristics?

Question

A pharmaceutical company in the final stages of designing a new nonsteroidal anti-inflammatory agent develops 2 different oral formulations of the drug.  Two groups of volunteers are each administered a different formulation, and average plasma drug levels are monitored over the next 12 hours.  The results are shown below:  Compared to the red curve, the formulation represented by the blue curve is most likely to have which of the following characteristics?

Quizplus · Accepted Answer

The above graph shows the plasma drug concentration-time curves of the 2 different oral formulations. The one represented by the blue curve shows a reduced and delayed peak level relative to the red curve, which is consistent with a sustained-release preparation. The absorption speed of an orally administered drug depends on the rate at which it dissolves in gastrointestinal fluids. Capsules and tablets can be designed with the active ingredient embedded in an insoluble matrix or encapsulated with coatings that dissolve at different rates to delay intestinal absorption. Slower drug absorption can have several advantages, including: These benefits make sustained-release preparations particularly useful for drugs with short half-lives (ie, allowing prolonged effect without need for multiple doses) or narrow therapeutic windows (ie, maintaining effective drug levels while minimizing absorption peaks). (Choice B) Enhanced CYP enzyme induction by the blue formulation would cause increased drug metabolism over time as additional enzymes are synthesized, leading to decreased serum drug levels. (Choice C) Increased biliary excretion of the blue formulation would be expected to decrease peak serum levels, but would not explain the delay in peak levels relative to the red curve. (Choice D) Drugs that are excreted into the bile can undergo enterohepatic cycling, which can prolong the drug's effect longer than expected given the drug's half-life. However, increased enterohepatic cycling would not explain the initial delay in peak serum levels seen in the blue curve. (Choice E) Reduced first-pass metabolism by the blue formulation would result in higher peak serum levels compared to the red curve due to increased quantities of drug entering the circulation. Educational objective: Sustained-release drug preparations have reduced and delayed peak levels compared to immediate-release preparations due to slower absorption in the gastrointestinal tract. Dampening of peak levels and prolonged absorption of the drug help maintain effective drug levels while minimizing toxicity.

A Pharmaceutical Company in the Final Stages of Designing a New