Define loading dose and provide the formula for an oral drug considering bioavailability.

• A. Loading dose = (Cmss * Vd) / F
• B. Loading dose = Cmss * Vd * F
• C. Loading dose = Cmss / (Vd * F)
• D. Loading dose = Cmss * F / Vd

Answer: (A)

The loading dose is the initial, larger dose given to rapidly achieve a target plasma concentration. For an oral drug, only a fraction F of each administered dose actually reaches the systemic circulation, while the amount that distributes into the body at steady state relates to Css × Vd. Setting the amount that enters circulation (Dose × F) equal to the amount needed in the body (Css × Vd) gives Dose × F = Css × Vd, so Dose = (Css × Vd) / F. This shows why the correct formula puts Vd in the numerator and F in the denominator: you must compensate for incomplete bioavailability to achieve the desired concentration quickly. If F were 1, as with IV administration, the loading dose simplifies to Css × Vd.