Amiodarone is a Class III antiarrhythmic but also has Class I, II and IV properties. Its major pharmacokinetic characteristic that explains why a loading dose is mandatory and toxicities persist long after drug withdrawal is:
- A Very short elimination half-life of 4–6 hours requiring frequent dosing
- B Narrow therapeutic index combined with zero-order (saturable) kinetics
- C Extremely large volume of distribution (~60 L/kg) and elimination half-life of 40–55 days ✓
- D Extensive first-pass hepatic extraction making oral bioavailability less than 5%
Correct answer: C. Extremely large volume of distribution (~60 L/kg) and elimination half-life of 40–55 days
Explanation
Amiodarone has an exceptionally large volume of distribution (~60 L/kg) due to its high lipophilicity and extensive tissue accumulation (lung, liver, thyroid, skin, cornea). Its elimination half-life is 40–55 days (some estimates even longer), meaning steady-state is only reached after months without loading; hence a high loading dose is given initially. Toxicities — pulmonary fibrosis, thyroid dysfunction, corneal microdeposits — persist for months after discontinuation because of this prolonged tissue retention.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.