Elimination Half-Life of Intravenous Diltiazem
The elimination half-life of diltiazem when administered as a continuous intravenous infusion is approximately 3.4 to 4.9 hours, with the half-life increasing as infusion rates increase due to nonlinear pharmacokinetics. 1
Pharmacokinetic Parameters for IV Diltiazem
Single Bolus Administration
- Following a single intravenous injection in healthy volunteers, diltiazem exhibits an elimination half-life of approximately 3.4 hours over a dose range of 10.5 to 21 mg 1
- The apparent volume of distribution is approximately 305 L, and systemic clearance averages 65 L/h 1
- In one study of healthy subjects receiving a bolus followed by infusion, the median elimination half-life was 206 minutes (3.4 hours), with a range of 144 to 452 minutes 2
Continuous Infusion Administration
- During constant rate intravenous infusion (4.8 to 13.2 mg/h for 24 hours), diltiazem exhibits nonlinear pharmacokinetics 1
- As the infusion dose increases, the elimination half-life increases from 4.1 to 4.9 hours 1
- Systemic clearance decreases from 64 to 48 L/h as infusion rates increase, while volume of distribution remains relatively unchanged (360 to 391 L) 1
Special Population Considerations
Patients with Atrial Fibrillation/Flutter
- In patients with atrial fibrillation or atrial flutter, diltiazem systemic clearance is decreased compared to healthy volunteers 1
- With bolus doses ranging from 2.5 to 38.5 mg, systemic clearance averaged 36 L/h 1
- During continuous infusions at 10 mg/h or 15 mg/h for 24 hours, systemic clearance averaged 42 L/h and 31 L/h respectively 1
Elderly Patients
- Diltiazem elimination is slower in elderly patients with hypertension 3
- After a 25 mg IV dose, clearance was 13 ± 4 ml/min/kg in elderly patients (mean age 68 years) compared to 23 ± 7 ml/min/kg in younger patients (mean age 30 years) 3
- Elimination half-lives were 4.5 ± 2.2 hours in elderly patients versus 3.8 ± 0.7 hours in younger patients after IV administration 3
- The decreased clearance in elderly patients is primarily due to reduced hepatic blood flow with age, as diltiazem has a high hepatic extraction ratio 4
Patients with Hepatic Dysfunction
- Diltiazem is extensively metabolized in the liver and has a high hepatic extraction ratio, making its clearance dependent primarily on hepatic blood flow 4, 1
- Liver cirrhosis reduces diltiazem's apparent clearance and prolongs its half-life 1
- Dose adjustments may be required in patients with hepatic impairment to minimize the risk of adverse drug reactions 4
Patients with Renal Dysfunction
- Renal insufficiency or end-stage renal disease does not significantly influence diltiazem disposition 1
- In patients undergoing continuous ambulatory peritoneal dialysis, the mean elimination half-life was 3.09 ± 1.16 hours, which did not differ from healthy volunteers 5
- Less than 0.1% of the administered dose is eliminated in dialysate over 24 hours 5
Clinical Implications
Metabolite Considerations
- Following single IV injection, plasma concentrations of N-monodesmethyldiltiazem and desacetyldiltiazem (two principal metabolites) are typically not detected 1
- However, these metabolites are observed following 24-hour constant rate infusion 1
- Total radioactivity measurements suggest the presence of other unidentified metabolites that attain higher concentrations than diltiazem and are more slowly eliminated, with a half-life of approximately 20 hours compared to 2-5 hours for diltiazem 1
Steady-State Considerations
- Constant rate IV infusions at 3,5,7, and 11 mg/h are predicted to produce steady-state plasma concentrations equivalent to 120,180,240, and 360 mg total daily oral doses respectively 1
- With long-term oral dosing, the elimination half-life increases to 6.3 ± 1 hour in young patients and 7.2 ± 2.1 hours in elderly patients 6