A clinical pharmacologist analyses the pharmacokinetics of a new drug. At steady state, plasma concentration fluctuates between a peak of 20 mg/L and a trough of 5 mg/L with 12-hourly dosing. The drug's therapeutic index is defined by an MEC of 4 mg/L and MTC of 25 mg/L. What percentage of the dosing interval does the drug concentration remain within the therapeutic range?

• A Approximately 50% of the dosing interval — concentration is therapeutic from the time it falls below MTC until it falls below MEC
• B 100% of the dosing interval — both peak and trough are within the therapeutic window (4–25 mg/L) ✓
• C Approximately 83% of the dosing interval — nearly the entire 12-hour interval, since peak barely exceeds MTC and trough is marginally above MEC
• D Only 67% — a third of time is spent at toxic levels above MTC because the peak exceeds the therapeutic range

Explanation

The therapeutic window is defined by MEC (minimum effective concentration) of 4 mg/L and MTC (maximum tolerated concentration) of 25 mg/L. The peak plasma concentration is 20 mg/L (below MTC of 25) and the trough is 5 mg/L (above MEC of 4). Since both the peak and the trough lie within the therapeutic window (4–25 mg/L), the drug concentration remains within the therapeutic range throughout the ENTIRE 12-hour dosing interval — 100% of the time. This is the ideal dosing scenario. The drug never exceeds the toxic threshold and never falls below efficacy, assuming mono-exponential pharmacokinetics between doses.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.