What is the half-life of IV Diltiazem (Cardizem)?

Half-Life of IV Diltiazem (Cardizem)

The elimination half-life of intravenous diltiazem is approximately 3.4 hours after a single bolus dose, but increases to 4-7 hours during continuous infusion due to nonlinear pharmacokinetics. 1

Pharmacokinetic Profile

Single Bolus Administration

• After a single IV injection in healthy volunteers, diltiazem demonstrates linear pharmacokinetics with a plasma elimination half-life of approximately 3.4 hours 1
• The apparent volume of distribution is approximately 305 L 1
• Systemic clearance averages approximately 65 L/h in healthy individuals 1

Continuous Infusion

• During constant rate IV infusion (4.8 to 13.2 mg/h for 24 hours), diltiazem exhibits nonlinear pharmacokinetics 1
• The elimination half-life increases from 4.1 to 4.9 hours as the infusion dose increases 1
• Systemic clearance decreases from 64 to 48 L/h with higher infusion rates 1

Patient-Specific Variations

Atrial Fibrillation/Flutter Patients

• In patients with atrial fibrillation or atrial flutter, the elimination half-life extends to 6.8-6.9 hours during continuous infusion (10-15 mg/h for 24 hours) 2
• Systemic clearance is reduced compared to healthy volunteers, averaging 31-42 L/h versus 65 L/h 1, 2
• This reduced clearance necessitates dose adjustments and closer monitoring in these patients 2

Hepatic Impairment

• Liver cirrhosis significantly reduces diltiazem's apparent oral clearance and prolongs its half-life 1
• Patients with hepatic dysfunction require careful dose titration and monitoring 1

Renal Impairment

• Renal insufficiency, even end-stage renal disease, does not appear to significantly influence diltiazem disposition 1
• No routine dose adjustment is required for renal dysfunction alone 1

Clinical Implications

Time to Steady State

• With a half-life of 3.4-7 hours, steady-state plasma concentrations are typically achieved after approximately 17-35 hours (5 half-lives) of continuous infusion 1

Duration of Effect

• Maximal hemodynamic effects usually occur within 2-5 minutes of bolus injection 1
• The median time to maximal heart rate reduction is approximately 4.3 minutes after starting infusion 3

Washout Period

• Complete drug elimination requires approximately 17-35 hours (5 half-lives) after discontinuation 1
• This extended washout period is clinically relevant when transitioning to other antiarrhythmic agents 1

Important Caveats

• The presence of metabolites (desacetyldiltiazem and N-desmethyldiltiazem) during continuous infusion contributes minimally to pharmacodynamic effects, as their plasma concentrations remain <15% and <10% of parent drug levels, respectively 2
• Total radioactivity measurements suggest unidentified metabolites with a half-life of approximately 20 hours exist, though their clinical significance remains unclear 1