Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6.

Article Details

Citation

Walsky RL, Astuccio AV, Obach RS

Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6.

J Clin Pharmacol. 2006 Dec;46(12):1426-38.

PubMed ID
17101742 [ View in PubMed
]
Abstract

Cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of drugs such as bupropion, efavirenz, propofol, and selegiline, among others. More than 200 commonly prescribed drugs and other xenobiotics were examined for their ability to inhibit CYP2B6-mediated bupropion hydroxylase activity. Thirty compounds were found exhibiting greater than 50% inhibition at 30 microM. Inhibitors of CYP2B6 were identified from a wide variety of therapeutic classes. The 2 platelet aggregation inhibitors, clopidogrel and ticlopidine, were both identified as potent inhibitors (IC50 = 0.0206 and 0.149 microM, respectively). Other inhibitors (IC50 < 1 microM) included clotrimazole, itraconazole, sertraline, and raloxifene. These in vitro data were used along with clinical pharmacokinetic information in the prediction of potential drug-drug interactions that could occur by inhibition of CYP2B6. Although few drugs tested are expected to cause drug interactions, clopidogrel and ticlopidine were identified as being of concern as potential inhibitors of clinical relevance. These findings are discussed in context to potential drug interactions that could be observed between these agents and drugs for which CYP2B6 is involved in metabolism.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
BupropionCytochrome P450 2B6ProteinHumans
Unknown
Substrate
Details
CisplatinCytochrome P450 2B6ProteinHumans
Unknown
Inhibitor
Details
ClotrimazoleCytochrome P450 2B6ProteinHumans
Unknown
Inhibitor
Inducer
Details
DoxorubicinCytochrome P450 2B6ProteinHumans
Unknown
Inhibitor
Details
EfavirenzCytochrome P450 2B6ProteinHumans
Unknown
Substrate
Inducer
Details
FluvoxamineCytochrome P450 2B6ProteinHumans
Unknown
Inhibitor
Details
ItraconazoleCytochrome P450 2B6ProteinHumans
Unknown
Inhibitor
Details
KetoconazoleCytochrome P450 2B6ProteinHumans
Unknown
Inhibitor
Details
NelfinavirCytochrome P450 2B6ProteinHumans
Unknown
Inhibitor
Details
ParoxetineCytochrome P450 2B6ProteinHumans
Unknown
Inhibitor
Details
QuinidineCytochrome P450 2B6ProteinHumans
Unknown
Inhibitor
Details
RaloxifeneCytochrome P450 2B6ProteinHumans
Unknown
Inhibitor
Details
RitonavirCytochrome P450 2B6ProteinHumans
No
Inhibitor
Inducer
Details
SelegilineCytochrome P450 2B6ProteinHumans
Unknown
Substrate
Inhibitor
Details
SertralineCytochrome P450 2B6ProteinHumans
Unknown
Substrate
Inhibitor
Details
SimvastatinCytochrome P450 2B6ProteinHumans
Unknown
Inhibitor
Inducer
Details
SulfaphenazoleCytochrome P450 2B6ProteinHumans
Unknown
Inhibitor
Details
TamoxifenCytochrome P450 2B6ProteinHumans
Unknown
Substrate
Inhibitor
Details
TiclopidineCytochrome P450 2B6ProteinHumans
Unknown
Inhibitor
Details
Drug Interactions
DrugsInteraction
Amitriptyline
Raloxifene
The metabolism of Amitriptyline can be decreased when combined with Raloxifene.
Amitriptyline
Memantine
The metabolism of Amitriptyline can be decreased when combined with Memantine.
Amitriptyline
Thiotepa
The metabolism of Amitriptyline can be decreased when combined with Thiotepa.
Amitriptyline
Nicotine
The metabolism of Amitriptyline can be decreased when combined with Nicotine.
Antipyrine
Raloxifene
The metabolism of Antipyrine can be decreased when combined with Raloxifene.
Antipyrine
Methimazole
The metabolism of Antipyrine can be decreased when combined with Methimazole.
Antipyrine
Memantine
The metabolism of Antipyrine can be decreased when combined with Memantine.
Antipyrine
Orphenadrine
The metabolism of Antipyrine can be decreased when combined with Orphenadrine.
Antipyrine
Rilpivirine
The metabolism of Antipyrine can be decreased when combined with Rilpivirine.
Antipyrine
Itraconazole
The metabolism of Antipyrine can be decreased when combined with Itraconazole.
Interactions
Improve patient outcomes
Build effective decision support tools with the industry’s most comprehensive drug-drug interaction checker.
Learn more