Seroquel

[Quetiapine]

Distribution

Quetiapine is widely distributed throughout the body with an apparent volume of distribution of 10± 4 L/ kg. It is 83% bound to plasma proteins at therapeutic concentrations. In vitro, quetiapine did not affect the binding of warfarin or diazepam to human serum albumin. In turn, neither warfarin nor diazepam altered the binding of quetiapine.

Metabolism and Elimination

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Following a single oral dose of 14 C-quetiapine, less than 1% of the administered dose was excreted as unchanged drug, indicating that quetiapine is highly metabolized. Approximately 73% and 20% of the dose was recovered in the urine and feces, respectively. Quetiapine is extensively metabolized by the liver. The major metabolic pathways are sulfoxidation to the sulfoxide metabolite and oxidation to the parent acid metabolite; both metabolites are pharmacologically inactive. In vitro studies using human liver microsomes revealed that the cytochrome P450 3A4 isoenzyme is involved in the metabolism of quetiapine to its major, but inactive, sulfoxide metabolite. Population Subgroups: Age: Oral clearance of quetiapine was reduced by 40% in elderly patients (³ 65 years, n= 9) compared to young patients (n= 12), and dosing adjustment may be necessary (See DOSAGE AND ADMINISTRATION).

Gender

There is no gender effect on the pharmacokinetics of quetiapine.

Race

There is no race effect on the pharmacokinetics of quetiapine.

Smoking

Smoking has no effect on the oral clearance of quetiapine.

Renal Insufficiency

Patients with severe renal impairment (Clcr= 10-30 mL/ min/ 1.73 m 2 , n= 8) had a 25% lower mean oral clearance than normal subjects (Clcr > 80 mL/ min/ 1.73 m 2 , n= 8), but plasma quetiapine concentrations in the subjects with renal insufficiency were within the range of concentrations seen in normal subjects receiving the same dose. Dosage adjustment is therefore not needed in these patients.

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