What is the half-life of Seroquel (quetiapine)?

Half-Life of Quetiapine (Seroquel)

Quetiapine has a mean terminal half-life of about 6 hours within the proposed clinical dose range. 1

Pharmacokinetic Profile

Quetiapine is rapidly absorbed after oral administration, reaching peak plasma concentrations in approximately 1.5 hours. The pharmacokinetic properties of quetiapine include:

• Bioavailability: 100% relative to solution form
• Protein binding: Approximately 83% bound to plasma proteins
• Metabolism: Extensively metabolized by the liver
  • Major metabolic pathways include sulfoxidation and oxidation
  • CYP3A4 is the primary enzyme involved in metabolism
• Elimination: Less than 1% excreted as unchanged drug
  • Approximately 73% recovered in urine
  • Approximately 20% recovered in feces

Half-Life Considerations

While the FDA label clearly states the mean terminal half-life is about 6 hours 1, other research has reported slightly different values:

• 7 hours according to some clinical pharmacokinetic studies 2
• 7-12 hours for the active metabolite, N-desalkyl quetiapine (norquetiapine) 1

Clinical Implications of Half-Life

The relatively short half-life of quetiapine has several important clinical implications:

1. Dosing Frequency: Despite the 6-hour half-life, quetiapine can be effectively administered twice daily rather than requiring more frequent dosing. Clinical studies have demonstrated that twice-daily (BD) dosing regimens are as effective as three-times-daily (TID) regimens 3.

2. Steady-State Concentrations: Steady-state concentrations are expected to be achieved within two days of dosing 1.

3. Receptor Occupancy: Interestingly, the receptor occupancy half-life differs from the plasma half-life:

   • Dopamine D2 receptor occupancy half-life: approximately 10 hours
   • Serotonin 5-HT2 receptor occupancy half-life: approximately 27 hours 4

This extended receptor occupancy may explain why the clinical efficacy extends beyond what would be expected from the plasma half-life alone.

Special Population Considerations

The half-life and clearance of quetiapine may be altered in certain populations:

• Elderly patients: Oral clearance reduced by 40% compared to younger patients 1
• Hepatic impairment: Dosage adjustment may be necessary
• Renal impairment: Severe renal impairment (CrCl = 10-30 mL/min) results in 25% lower mean oral clearance 1

Common Pitfalls

1. Assuming plasma half-life equals duration of clinical effect: The receptor occupancy half-life is longer than the plasma half-life, which explains why twice-daily dosing is effective despite the relatively short plasma half-life.

2. Overlooking age-related changes: Elderly patients have reduced clearance and may require lower doses.

3. Neglecting drug interactions: Medications that induce or inhibit CYP3A4 can significantly affect quetiapine levels and potentially alter its effective half-life.

Quetiapine's unique pharmacokinetic and pharmacodynamic profile allows for twice-daily dosing despite its relatively short plasma half-life, making it a convenient option for patients requiring antipsychotic therapy.