Quetiapine Ketoconazole

Cyt 3A3/4 metabolizes clozapine, sertindole, quetiapine common substrates -tricyclic antidepressants, nefazodone, sertraline, carbamazepine, ethosuximide, terfenadine, benzodiazepines, diltiazem, nifedipine, verapamil, erythromycin, cyclosporine, lidocaine, quinidine, cisapride, paracetamol. Common inhibitors -nefazodone, fluvoxamine, fluoxetine, ketoconazole. 

After single-dose administration, the mean bioavailability of quetiapine is 9% with significant interindividual variation. If a CYP 3A4 inhibitor (e.g., cimetidine, ketoconazole, nefazodone, grapefruit juice, or erythromycin) is added to quetiapine, increased side effects (e.g., sedation or orthostasis) may occur. Fluoxetine may also decrease clearance of a medication such as quetiapine metabolized through CYP 3A4. However, with fluoxetine, it is the long-acting metabolite norfluoxetine, and not fluoxetine, that is the primary inhibitor of 3 A4 metabolism. If an enzyme inducer such as carbamazepine or St. lohn s wort is added to quetiapine, then decreased antipsychotic effects may occur. ... 

Grimm SW, RichtandNM, Winter HR, Stams KR, Reele SB. Effects of cytochrome P450 3A modulators ketoconazole and carbamazepine on quetiapine pharmacokinetics. BrJ Clin Pharmacol (2006), 61, 58-69,... 

The plasma levels of quetiapine are increased by erythromycin and ketoconazole. Azoles, macrolides, and protease inhibitors are expected to interact similarly. 

Twelve healthy subjects received a single 25-mg dose of quetiapine on day 4 of a 4 day course of ketoconazole 200 mg daily. The AUC and maximum plasma levels of quetiapine were inereased by 522% and 235%, respectively, and the mean half-life of quetiapine was inereased from 2.61 to 6.76 hours. Ketoconazole is a potent inhibitor of the eytoehrome P450 isoenzyme CYP3A4 by which quetiapine is metabolised. Coneurrent use... 

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