Paroxetine Half-Life
Paroxetine has an elimination half-life of approximately 21 hours (with a coefficient of variation of 32%) after steady-state dosing, making once-daily administration appropriate. 1
Pharmacokinetic Details
Half-Life Characteristics
- The mean elimination half-life is 21 hours at steady state after 30 days of daily dosing with 30 mg tablets 1
- There is substantial interindividual variability, with reported ranges from 7 to 65 hours in healthy young subjects 2
- This 24-hour approximate half-life supports once-daily dosing and allows steady-state concentrations to be achieved within a reasonable timeframe 3
Time to Steady State
- Steady-state plasma concentrations are generally achieved within 7 to 14 days, though it may take substantially longer in occasional patients 1, 2
- Approximately 10 days is typical for most subjects to reach steady state 1
Clinical Implications of Paroxetine's Half-Life
Comparison to Other SSRIs
- Paroxetine's half-life is significantly shorter than fluoxetine (which has a 2-4 day half-life with an active metabolite lasting 7-15 days), making dose adjustments more predictable 3
- The half-life is similar to sertraline (approximately 24 hours) but paroxetine exhibits nonlinear pharmacokinetics at higher doses due to saturable metabolism, unlike sertraline 4, 3
- This half-life range (21-36 hours among SSRIs excluding fluoxetine) is consistent across most SSRIs except fluoxetine 4
Therapeutic Drug Monitoring Considerations
- Blood samples for therapeutic drug monitoring should be collected at steady state (at least 5 half-lives after dose changes), which for paroxetine means approximately 1 week after stable dosing 5
- Sampling should occur 12-16 hours after the last dose (or 24 hours if dosed once daily) during the terminal elimination phase 5
Important Caveats
- The half-life becomes longer at higher doses due to paroxetine's inhibition of its own clearance via saturable CYP2D6 metabolism 3, 1
- Elderly patients show significantly slower elimination with higher plasma concentrations than younger subjects, though with wide interindividual variation and overlap 1, 2
- Severe renal impairment (creatinine clearance <30 mL/min) results in approximately 4-fold higher plasma concentrations, and hepatic impairment causes approximately 2-fold increases, both affecting effective half-life 1