From the Guidelines
Seroquel (quetiapine) is primarily cleared from the body through liver metabolism, specifically by the cytochrome P450 3A4 enzyme system. This process involves extensive first-pass metabolism in the liver, resulting in the production of several metabolites, including the pharmacologically active N-desalkylquetiapine (norquetiapine) 1. The liver's role in metabolizing quetiapine is crucial, as indicated by the changes in pharmacokinetic parameters with age, including decreased liver mass and hepatic blood flow, which can affect the biotransformation of highly metabolized drugs like quetiapine 1.
After metabolism, the majority of the drug, approximately 73%, is excreted in urine, while about 20% is excreted in feces. The elimination half-life of quetiapine is relatively short, averaging about 6 hours for the immediate-release formulation and about 7 hours for the extended-release version. This rapid clearance means that most of the drug is eliminated from the body within 1-2 days after the last dose.
Key factors influencing quetiapine clearance include liver function and the presence of medications that interact with the CYP3A4 enzyme system. Patients with liver impairment may experience higher blood levels of the medication due to reduced metabolic capacity and may require dose adjustments. Similarly, medications that inhibit or induce CYP3A4 can significantly affect quetiapine levels in the body, potentially leading to increased side effects or reduced efficacy. Understanding these factors is essential for optimizing quetiapine therapy and minimizing adverse effects.
From the FDA Drug Label
Quetiapine and its metabolites are non-inhibitors of major metabolizing CYP’s (1A2, 2C9, 2C19, 2D6 and 3A4). The mean plasma clearance of quetiapine was reduced by 30% to 50% in elderly patients when compared to younger patients Since quetiapine is extensively metabolized by the liver, higher plasma levels are expected in patients with hepatic impairment.
Seroquel (quetiapine) is cleared by the liver through the cytochrome P450 enzyme system, specifically CYP3A4. The drug is extensively metabolized by the liver, and its clearance may be affected by factors such as age, renal impairment, and hepatic impairment.
- Key factors that influence quetiapine clearance include:
- Liver function: Quetiapine is extensively metabolized by the liver, and higher plasma levels are expected in patients with hepatic impairment.
- Age: The mean plasma clearance of quetiapine is reduced by 30% to 50% in elderly patients compared to younger patients.
- Drug interactions: Quetiapine exposure is increased by CYP3A4 inhibitors and decreased by CYP3A4 inducers 2.
From the Research
Metabolism and Clearance of Seroquel
Seroquel, also known as quetiapine, is primarily cleared by the body through hepatic metabolism. The key points regarding its clearance are:
- Quetiapine is approximately 83% bound to serum proteins 3.
- The primary route of elimination is through hepatic metabolism, with cytochrome P450 3A4 (CYP3A4) being the dominant enzyme responsible for its metabolism 3, 4.
- After administration, approximately 73% of the radioactivity is excreted in the urine and 21% in faeces, with quetiapine accounting for less than 1% of the excreted radioactivity 3.
- Eleven metabolites have been identified, with two being pharmacologically active but circulating at concentrations unlikely to contribute substantially to the drug's effects 3.
- The active metabolite of quetiapine, N-desalkylquetiapine, is mainly formed by CYP3A4 and is further metabolized by both CYP2D6 and CYP3A4, with CYP2D6 showing a preference for its metabolism 5.
Factors Influencing Clearance
Several factors can influence the clearance of quetiapine, including:
- Age: Oral clearance declines with age 3.
- Hepatic dysfunction: Clearance may be reduced in patients with hepatic impairment 3.
- Drug interactions: Phenytoin and thioridazine increase the clearance of quetiapine, while ketoconazole decreases its clearance 3.
- CYP3A4 inhibitors or inducers: May require dosage adjustment of quetiapine due to their effect on its metabolism 3, 4.