The Effect of Multiple Doses of Cimetidine on the Steady-State Pharmacokinetics of Quetiapine in Men With Selected Psychotic Disorders

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Abstract
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.