The effects of concomitant phenytoin administration on the steady-state pharmacokinetics of quetiapine

Quetiapine fumarate ('Seroquel') is a newly introduced atypical antipsychot ic with demonstrated efficacy in the treatment of positive and negative sym ptoms of schizophrenia. It is extensively metabolized, predominantly by cyt ochrome 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 i ndeed have a marked effect on the metabolism of quetiapine, resulting in a 5-fold increase in clearance when administered concomitantly to patients wi th DSM-IV-diagnosed schizophrenia, schizoaffective disorder, or bipolar dis order. These results indicate that dosage adjustment of quetiapine may be n ecessary 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.