In vitro studies on quetiapine metabolism using the substrate depletion approach with focus on drug-drug interactions
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In vitro studies on quetiapine metabolism using the substrate depletion approach with focus on drug-drug interactions. / Hasselstøm, Jørgen; Linnet, Kristian.
I: Drug Metabolism and Drug Interactions, Bind 21, Nr. 3-4, 06.07.2006, s. 187-211.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - In vitro studies on quetiapine metabolism using the substrate depletion approach with focus on drug-drug interactions
AU - Hasselstøm, Jørgen
AU - Linnet, Kristian
PY - 2006/7/6
Y1 - 2006/7/6
N2 - 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 μM 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.
AB - 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 μM 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.
KW - Drug-drug interactions
KW - Metabolism
KW - Quetiapine
KW - Substrate depletion
UR - http://www.scopus.com/inward/record.url?scp=33745668220&partnerID=8YFLogxK
M3 - Journal article
C2 - 16841513
AN - SCOPUS:33745668220
VL - 21
SP - 187
EP - 211
JO - Drug Metabolism and Drug Interactions
JF - Drug Metabolism and Drug Interactions
SN - 2363-8907
IS - 3-4
ER -
ID: 230033026