How Long Does Seroquel (Quetiapine) Stay in Your System?
Seroquel (quetiapine) has a plasma elimination half-life of approximately 6-7 hours, meaning it takes roughly 1.5-2 days (30-35 hours) for the drug to be essentially cleared from your system after stopping treatment. 1, 2
Pharmacokinetic Timeline
Elimination Half-Life
- The terminal plasma elimination half-life is approximately 7 hours in most adults, though this represents the time for plasma concentrations to decrease by half, not complete elimination 1
- After oral administration, quetiapine is rapidly absorbed with peak plasma concentrations occurring 1-2 hours after dosing 1
- Complete elimination from the body typically requires 5-6 half-lives, which translates to approximately 30-42 hours (1.5-2 days) for quetiapine 1, 3
Metabolism and Excretion
- Quetiapine is extensively metabolized in the liver, primarily by cytochrome P450 3A4 1
- After administration of radiolabeled quetiapine, approximately 73% of radioactivity is excreted in urine and 21% in feces 1
- Less than 1% of quetiapine is excreted unchanged, indicating nearly complete hepatic metabolism before elimination 1
- Eleven metabolites have been identified, with two being pharmacologically active but circulating at only 2-12% of parent drug concentrations 1
Receptor Occupancy vs. Plasma Levels
An important distinction exists between plasma drug levels and clinical effects: dopamine D2 receptor occupancy persists longer than plasma concentrations would predict. 4
- At 2 hours after the last dose, dopamine D2 receptor occupancy is 44% in the striatum 4
- Receptor occupancy half-life is approximately 10 hours—nearly twice as long as the plasma half-life 4
- After 26 hours, D2 receptor occupancy returns to baseline levels similar to untreated individuals 4
- Serotonin 5-HT2 receptor blockade shows even more prolonged effects, with 72% occupancy at 2 hours declining to 50% at 26 hours, with a receptor occupancy half-life of 27 hours 4
Factors Affecting Elimination
Patient-Specific Variables
- Oral clearance declines with age, requiring longer elimination times in elderly patients 1
- Hepatic dysfunction reduces clearance by approximately 50% in patients with severe liver disease, potentially doubling elimination time 1
- Renal impairment does not significantly affect quetiapine pharmacokinetics, as hepatic metabolism is the primary elimination route 1
- Cigarette smoking does not alter quetiapine pharmacokinetics 1
Drug Interactions Affecting Clearance
- Phenytoin and thioridazine increase quetiapine clearance (as CYP3A4 inducers), shortening elimination time 1
- Ketoconazole decreases clearance (as a CYP3A4 inhibitor), prolonging elimination time 1
- Cimetidine, haloperidol, risperidone, and imipramine have no clinically significant effects on quetiapine elimination 1
Clinical Implications
Dosing Frequency
- Despite the 6-7 hour half-life, quetiapine can be effectively administered twice daily rather than three times daily, as demonstrated in clinical trials showing therapeutic equivalence between 225 mg twice daily and 150 mg three times daily 5
- This twice-daily dosing is supported by the prolonged receptor occupancy relative to plasma levels 4