In vitro studies on quetiapine metabolism using the substrate depletion approach with focus on drug-drug interactions.

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Hasselstrom J, Linnet K

In vitro studies on quetiapine metabolism using the substrate depletion approach with focus on drug-drug interactions.

Drug Metabol Drug Interact. 2006;21(3-4):187-211.

PubMed ID

16841513 [ View in PubMed

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Abstract

The metabolism of the atypical antipsychotic quetiapine was investigated by in vitro methods. Pharmacokinetic parameters were determined in human liver microsomes and recombinant cytochrome P450 measuring substrate depletion and product formation. The cytochrome P450 isozymes CYP3A4 and CYP2D6 displayed activity towards quetiapine. The isozyme CYP2D6 played a minor role in the metabolism of quetiapine as CYP3A4 contributed 89% to the overall metabolism. A Km value of 18 microM was determined by substrate depletion, suggesting linear kinetics under therapeutic conditions. Drugs known to inhibit CYP3A4, such as ketoconazole and nefazodone, displayed almost complete inhibition at low concentrations, whereas inhibitors of CYP2D6 do not seem to have a clinically relevant effect.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Quetiapine	Cytochrome P450 2D6	Protein	Humans	Unknown	Substrate	Details