Paroxetine Half-Life
The elimination half-life of paroxetine is approximately 21 hours (with a coefficient of variation of 32%) after steady-state dosing, which supports once-daily administration. 1
Pharmacokinetic Profile
Steady-state concentrations are typically achieved by approximately 10 days for most patients, though it may take substantially longer in occasional patients. 1
- At steady state following 30 mg daily dosing for 30 days, the mean elimination half-life was 21.0 hours (CV 32%). 1
- The 24-hour half-life permits once-daily dosing in clinical practice. 2
- Paroxetine has no active metabolites, as the principal metabolites have no more than 1/50 the potency of the parent compound at inhibiting serotonin uptake. 1
Clinical Implications of Half-Life
For therapeutic drug monitoring, blood samples should be collected at steady state (approximately 1 week after stable dosing), with sampling occurring 12-16 hours after the last dose or 24 hours if dosed once daily. 3
Nonlinear pharmacokinetics occur with paroxetine due to saturation of CYP2D6-mediated metabolism:
- Steady-state drug exposure (AUC0-24) is about 8 times greater than predicted from single-dose data. 1
- At steady state, Cmax and Cmin values are about 6 and 14 times what would be predicted from single-dose studies. 1
- This excess accumulation results from saturation of one of the enzymes that metabolizes paroxetine. 1
Special Population Considerations
Elderly patients show 70-80% greater Cmin concentrations compared to non-elderly subjects at equivalent doses, necessitating initial dose reduction. 1
Renal impairment: Patients with creatinine clearance below 30 mL/min have approximately 4-fold greater mean plasma concentrations than normal volunteers, while those with creatinine clearance 30-60 mL/min show about 2-fold increases. 1
Hepatic impairment: Patients with hepatic functional impairment demonstrate about a 2-fold increase in plasma concentrations (AUC, Cmax). 1
Metabolism and Excretion
- Approximately 64% of an oral dose is excreted in urine (2% as parent compound, 62% as metabolites) over 10 days post-dosing. 1
- About 36% is excreted in feces (mostly as metabolites, less than 1% as parent compound). 1
- Paroxetine metabolism is mediated in part by CYP2D6, and paroxetine itself is both a substrate and potent inhibitor of this enzyme. 1, 4