Trazodone Half-Life
The elimination half-life of trazodone is approximately 7-9 hours in healthy adults, though this can extend to 10-12 hours depending on the study population. 1, 2
Pharmacokinetic Details
The half-life of trazodone has been consistently documented across multiple studies:
- Terminal elimination half-life ranges from 7.3 to 8.6 hours in healthy human subjects after oral administration 2
- One early pharmacokinetic study reported a biphasic elimination pattern with a redistribution half-life of approximately 1 hour and an elimination half-life of 10-12 hours 1
- Another study described the biphasic elimination as 4.4 hours for the first 10 hours and 7.5 hours for the next 24 hours 3
- After intravenous administration in horses (for comparative reference), the elimination half-life was 8.58 hours, with terminal phase half-life of 7.11 hours after oral administration 4
Clinical Implications for Dosing
Despite the relatively short half-life of 7-9 hours, trazodone's clinical duration of action for sedation is only 6-8 hours, which is why it requires multiple daily doses for continuous therapeutic effect. 5, 6
Key dosing considerations:
- The 3- to 9-hour half-life favors dose-weighting at bedtime for patients using trazodone as an antidepressant 6
- Single nighttime dosing (150 mg predominantly at bedtime, increased to 200-300 mg as needed) is equally effective as multiple daily dosing for depression treatment 6
- For patients with PTSD-related nightmares, the mean effective dose was 212 mg/day, though the dosing frequency was not specified in the guideline 5
Absorption and Metabolism
- Trazodone is nearly completely absorbed after oral administration 1
- Food delays absorption and reduces peak serum concentration (from 1.88 to 1.47 mcg/mL) but does not alter total bioavailability (approximately 63-65%) 2
- Less than 0.13% is excreted unchanged in urine, indicating extensive hepatic metabolism 2
- The drug is metabolized hepatically by hydroxylation and oxidation to probably inactive metabolites 1