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Quetiapine fumarate ('Seroquel') is a newly introduced atypical antipsychotic with demonstrated efficacy in the treatment of positive and negative symptoms of schizophrenia. It is extensively metabolized, predominantly by cytochrome P450 3A4. Therefore, concurrent administration of drugs that induce or inhibit this enzyme may affect quetiapine pharmacokinetics. This study demonstrated that the potent cytochrome P450 enzyme-inducer phenytoin did indeed have a marked effect on the metabolism of quetiapine, resulting in a 5-fold increase in clearance when administered concomitantly to patients with DSM-IV-diagnosed schizophrenia, schizoaffective disorder, or bipolar disorder. These results indicate that dosage adjustment of quetiapine may be necessary when the two drugs are given concurrently and that caution may be required when administering other drugs that inhibit or induce cytochromes, particularly P450 3A4.

Quetiapine fumarate (Seroquel) is an atypical antipsychotic agent approved for the treatment of psychosis. It is extensively metabolized by the CYP450 3A4 isozyme. The principal aim of the study was to investigate the effect of multiple doses of cimetidine, a nonspecific P450 inhibitor, on the steady-state pharmacokinetics of quetiapine. Thirteen patients (seven completers) with selected psychotic disorders received escalating doses of quetiapine from 25 to 150 mg three times daily on days 3 to 8 and were then maintained at 150 mg three times daily until day 19. Cimetidine (400 mg) was initiated on the afternoon of day 15 and administered three times daily with every dose of quetiapine thereafter. Quetiapine plasma concentrations were measured before and after cimetidine coadministration, and quetiapine pharmacokinetic parameters were calculated. Of the 13 men who entered the study, seven completed it. A slight increase in quetiapine plasma levels and reduction in oral clearance were observed after cimetidine coadministration. No serious adverse events were observed during quetiapine treatment. No clinically relevant alterations in quetiapine pharmacokinetics were observed after cimetidine coadministration in patients with psychotic disorders.

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