Under first-order elimination with multiple dosing, which factors determine the peak and trough at steady state?

• A. Dose, dosing interval, and clearance.
• B. Dose only.
• C. Volume of distribution alone.
• D. Bioavailability alone.

Answer: (A)

When a drug obeys first-order elimination and is given repeatedly, the concentrations at steady state reflect a balance between what you put in each dose and how fast you remove it. The peak (end of dose interval) and trough (just before the next dose) are set by three factors: how large the dose is, how often you give it (the dosing interval), and how quickly the body clears the drug (clearance). A larger dose raises both peak and trough; shortening the interval increases accumulation and raises both values; higher clearance removes drug faster and lowers the cycle, reducing the peaks and troughs. Bioavailability only matters if you’re not giving the drug IV, and volume of distribution influences the rate of elimination (through k = Cl/Vd) but does not by itself replace the three direct determinants above. In short, dose, dosing interval, and clearance determine the steady-state peak and trough.