PK/PD in Medicine: Amiodarone

Amiodarone is an antiarrhythmic drug indicated for treatment and prophylaxis of ventricular fibrillation (VF)* and hemodynamically unstable congestive ventricular tachycardia (VT)* Pharmacology: Amiodarone is a class III antiarrhythmic drug. Mechanism : Inhibition of potassium rectifier currents responsible for repolarizing the heart during phase 3 of cardiac action potential. K+ channel-blocking effect results in increased action potential duration and a prolonged effective refractory period in cardiac myocytes.

Amiodarone is administered intravenously (infusions) & orally in humans. The recommended starting dose is about 1000 mg over the first 24 hours of therapy given as a sequence of infusions.

Amiodarone displays 4 compartment behaviour, with very high Vss (because of high LogP), very low systemic clearance (due to low intrinsic clearance & high PPB), a long terminal elimination half-life (t1/2 =0.693*Vss/CL). The long t1/2 of 47 days means it will take 235 days to reach steady state & 235 days for it be completely eliminated from the body post cessation of therapy. Its pharmacological effect will persist post therapy and also has drug-drug interaction potential if other medications are taken during this period.