True or false: If a drug has an active metabolite, it is likely that plasma concentration does not correlate with response.

True or false: If a drug has an active metabolite, it is likely that plasma concentration does not correlate with response.

• A. False
• B. Uncertain
• C. Not applicable
• D. True

Answer: (D)

When a drug has an active metabolite, the pharmacologic effect often depends on both the parent drug and the metabolite. The metabolite can contribute significantly to activity, have a different potency, and persist longer or form at different rates than the parent. Because of these differences, the amount of parent drug in plasma may not track how strong the overall effect will be. Individual variations in metabolism (genetics, drug interactions, organ function) can change how much metabolite is produced, further decoupling parent concentration from response. Additionally, there can be a time lag between changes in parent levels and the metabolite-driven effect. All of this makes plasma concentration of the parent a poor predictor of response when an active metabolite is involved.

When a drug has an active metabolite, the pharmacologic effect often depends on both the parent drug and the metabolite. The metabolite can contribute significantly to activity, have a different potency, and persist longer or form at different rates than the parent. Because of these differences, the amount of parent drug in plasma may not track how strong the overall effect will be. Individual variations in metabolism (genetics, drug interactions, organ function) can change how much metabolite is produced, further decoupling parent concentration from response. Additionally, there can be a time lag between changes in parent levels and the metabolite-driven effect. All of this makes plasma concentration of the parent a poor predictor of response when an active metabolite is involved.