A patient requires a loading dose of digoxin to achieve rapid therapeutic plasma levels. The loading dose is calculated primarily based on:
- A The target plasma concentration multiplied by the volume of distribution (Vd), as the loading dose must fill the entire apparent distribution volume to achieve the target level ✓
- B The drug's half-life (t1/2), because more drug is needed to saturate enzyme systems before steady-state is reached
- C The drug's clearance (CL) and bioavailability (F), as the loading dose must equal the first steady-state trough level
- D The drug's protein binding fraction, since the loading dose must saturate plasma proteins before free drug reaches the therapeutic range
Explanation
Loading dose = (Target Cp × Vd) / F, where Cp is target plasma concentration, Vd is volume of distribution, and F is bioavailability. The concept is that the loading dose must distribute into the full apparent volume of distribution (Vd) to achieve the desired plasma concentration immediately, bypassing the time needed to accumulate drug over multiple half-lives. Digoxin has a very large Vd (~500–700 L/70 kg) due to extensive tissue binding, requiring relatively large loading doses (0.5–1 mg IV) despite low therapeutic plasma concentrations (0.5–2 ng/mL). Maintenance dose is determined by clearance: MD = CL × target Cp (average steady-state) × dosing interval / F.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.