A drug with a very large volume of distribution is given a loading dose to rapidly achieve target plasma concentration. Which formula correctly calculates the loading dose?

• A. loading dose = target plasma concentration × clearance
• B. loading dose = target plasma concentration × volume of distribution
• C. loading dose = target concentration / bioavailability
• D. loading dose = target plasma concentration × half-life

Answer: (B)

The key idea is that a loading dose is based on how much drug must be in the body to achieve the desired plasma level, which is determined by the volume of distribution. The amount of drug in the body equals the target plasma concentration times the apparent volume that distributes the drug (Vd). If the drug is given IV, bioavailability is effectively 1, so the loading dose equals Cp × Vd. A very large Vd means a large amount is required to raise the plasma concentration quickly, which is exactly why the formula Cp × Vd is used for the loading dose in this scenario.

The other approaches miss the mechanism: relying on clearance addresses elimination and maintenance, not the initial amount needed to reach the target concentration; dividing by bioavailability ignores how widely the drug distributes; and using half-life ties to elimination timing rather than the total dose needed to achieve a given level.