Pharmaceutical Half-Life of Trazodone and Bupropion (Wellbutrin)
Trazodone has an elimination half-life of 7-13 hours in adults with normal liver function, while bupropion (Wellbutrin) has a shorter half-life of 5-9 hours in younger adults (20-45 years) that extends to 11-13 hours in elderly patients.
Trazodone Pharmacokinetics
Elimination Half-Life
- The terminal elimination half-life of trazodone ranges from 7.3 to 13 hours in healthy adults with normal hepatic function 1, 2, 3.
- A well-controlled study in 43 healthy subjects demonstrated a mean elimination half-life of 4.7 hours in young men (18-40 years), which increased to 8.2 hours in elderly men (60-76 years) 4.
- Women showed similar age-related increases, with half-life extending from 5.9 hours in young women to 7.6 hours in elderly women 4.
Factors Affecting Trazodone Half-Life
- Obesity significantly prolongs trazodone's half-life to 13.3 hours (compared to 5.9 hours in normal-weight individuals) due to increased volume of distribution, though clearance remains unchanged 4.
- The biphasic elimination pattern includes a redistribution half-life of approximately 1 hour followed by the terminal elimination phase of 10-12 hours 1, 3.
- Food intake does not alter the total bioavailability (63-65%) but delays absorption and reduces peak serum concentrations 2.
Clinical Implications for Trazodone
- Trazodone is nearly completely metabolized hepatically through hydroxylation and oxidation to inactive metabolites 1.
- Less than 0.13% of the administered dose is excreted unchanged in urine, indicating extensive hepatic metabolism 2.
- Elderly men show reduced clearance (1.65 vs. 2.31 ml/min/kg in young men), necessitating potential dosage reduction during chronic therapy 4.
Bupropion (Wellbutrin) Pharmacokinetics
Elimination Half-Life
- Bupropion has an elimination half-life of 5-9 hours in young healthy individuals (age 20-45 years) 5.
- In elderly patients, the half-life extends to 11-13 hours 5.
Active Metabolites
- Bupropion is extensively metabolized into three active metabolites: hydroxybupropion, threohydrobupropion, and erythrohydrobupropion, each with substantial antidepressant activity 6.
- These active metabolites contribute to the overall pharmacological effect and may have longer half-lives than the parent compound 6.
Clinical Dosing Considerations
- The maximum dose is 450 mg per day for immediate-release formulations and 400 mg per day for sustained-release formulations due to seizure risk 6.
- Bupropion is the only antidepressant with no appreciable activity on serotonin, working primarily through norepinephrine and dopamine neurotransmitters 6.
Key Clinical Distinctions
Comparative Half-Life Summary
- Trazodone: 7-13 hours (longer in elderly and obese patients) 1, 2, 3, 4
- Bupropion: 5-9 hours (young adults) to 11-13 hours (elderly) 5
Practical Dosing Implications
- Trazodone's longer half-life allows for once or twice-daily dosing, with steady-state achieved after approximately 5 half-lives (35-65 hours) 5.
- Both medications require dose adjustments in elderly patients due to prolonged elimination 5, 4.
- For trazodone, dosing should be based on ideal body weight in obese patients rather than total body weight due to the dramatically increased volume of distribution 4.