What is the loading dose for a drug with a target Css and known Vd and F?

• A. Loading dose = Css × Vd / F
• B. Loading dose = Css × F / Vd
• C. Loading dose = Css × Vd × F
• D. Loading dose = Css / (Vd × F)

Answer: (A)

Loading dose is the amount of drug needed to rapidly reach the target steady-state concentration (Css) using the known volume of distribution (Vd) and bioavailability (F). In a one-compartment view, the amount of drug in the body at Css equals Css × Vd. Because only a fraction F of an extravascular dose reaches systemic circulation, you must divide that amount by F to give a dose that will achieve Css. Therefore, loading dose = Css × Vd / F. If the drug is given intravenously (F = 1), this simplifies to Css × Vd. After this initial bolus, a maintenance dosing rate is used to keep Css at the target, with rate = Css × Cl / F. For example, targeting Css = 2 mg/L, Vd = 50 L, F = 0.8 gives LD = 2 × 50 / 0.8 = 125 mg.