Regulation of drug-metabolizing cytochrome P450 enzymes by glucocorticoids.

Article Details

Citation

Dvorak Z, Pavek P

Regulation of drug-metabolizing cytochrome P450 enzymes by glucocorticoids.

Drug Metab Rev. 2010 Nov;42(4):621-35. doi: 10.3109/03602532.2010.484462.

PubMed ID
20482443 [ View in PubMed
]
Abstract

The regulation of drug-metabolizing cytochrome P450 enzymes (CYP) is a complex process involving multiple mechanisms. Among them, transcriptional regulation through ligand-activated nuclear receptors is the crucial mechanism involved in hormone-controlled and xenobiotic-induced expression of drug-metabolizing CYPs. In this article, we focus, in detail, on the role of the glucocorticoid receptor (GR) in the transcriptional regulation of human drug-metabolizing CYP enzymes and the mechanisms of the regulation. There are at least three distinct transcriptional mechanisms by which GR controls the expression of CYPs: 1) direct binding of GR to a specific gene-promoter sequence called the glucocorticoid responsive element (GRE); 2) indirect binding of GR in the form of a multiprotein complex to gene promoters without a direct contact between GR and promoter DNA; and 3) up- or downregulation of other CYP transcriptional regulators or nuclear receptors (i.e., transcriptional regulatory cross-talk). However, due to the general effect of glucocorticoids on numerous cellular pathways and functions, the net transcriptional effect of glucocorticoids on drug-metabolizing enzymes is usually a combination of several mechanisms. Since synthetic glucocorticoids are widely prescribed in human pharmacotherapy for the treatment of many diseases, comprehensive understanding of the transcriptional regulation of drug-metabolizing CYPs via GR with respect to glucocorticoid therapy or glucocorticoid hormonal status will aid in the development of efficient individualized pharmacotherapy without drug-drug interactions.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
AmcinonideCytochrome P450 3A4ProteinHumans
No
Substrate
Inducer
Details
AmcinonideCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
BetamethasoneCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
Betamethasone phosphateCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inducer
Details
Betamethasone phosphateCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
CiclesonideCytochrome P450 3A4ProteinHumans
No
Substrate
Details
ClobetasolCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
Clobetasol propionateCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
Clocortolone acetateCytochrome P450 3A4ProteinHumans
Unknown
Inducer
Details
Clocortolone acetateCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
CloprednolCytochrome P450 3A4ProteinHumans
Unknown
Inducer
Details
CloprednolCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
CortisoneCytochrome P450 3A4ProteinHumans
Unknown
Inducer
Details
CortisoneCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
Cortisone acetateCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
CortivazolCytochrome P450 3A4ProteinHumans
Unknown
Inducer
Details
CortivazolCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
DeflazacortCytochrome P450 3A4ProteinHumans
No
Substrate
Inducer
Details
DeflazacortCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
Dexamethasone isonicotinateCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
DifluocortoloneCytochrome P450 3A4ProteinHumans
No
Substrate
Inducer
Details
FluocinonideCytochrome P450 3A4ProteinHumans
No
Substrate
Inducer
Details
FluocinonideCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
FluocortoloneCytochrome P450 3A4ProteinHumans
No
Substrate
Inducer
Details
FluocortoloneCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
FluorometholoneCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inducer
Details
FluorometholoneCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
FluprednideneCytochrome P450 3A4ProteinHumans
No
Substrate
Inducer
Details
FluprednideneCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
Fluprednidene acetateCytochrome P450 3A4ProteinHumans
No
Inducer
Details
Fluprednidene acetateCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
FluticasoneCytochrome P450 3A4ProteinHumans
No
Substrate
Inhibitor
Inducer
Details
FluticasoneCytochrome P450 3A5ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
Fluticasone furoateCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
Fluticasone furoateCytochrome P450 3A5ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
HalometasoneCytochrome P450 3A4ProteinHumans
Unknown
Inducer
Details
HalometasoneCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
MedrysoneCytochrome P450 3A4ProteinHumans
No
Substrate
Inducer
Details
MedrysoneCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
Melengestrol acetateCytochrome P450 3A4ProteinHumans
Unknown
Inducer
Details
Melengestrol acetateCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
MeprednisoneCytochrome P450 3A4ProteinHumans
No
Substrate
Inducer
Details
MeprednisoneCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
Methylprednisolone hemisuccinateCytochrome P450 3A4ProteinHumans
Unknown
Inducer
Details
Methylprednisolone hemisuccinateCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
MometasoneCytochrome P450 3A4ProteinHumans
No
Substrate
Inducer
Details
MometasoneCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
Mometasone furoateCytochrome P450 3A4ProteinHumans
No
Substrate
Inducer
Details
Mometasone furoateCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
ParamethasoneCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
ParamethasoneCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
Prednisolone hemisuccinateCytochrome P450 3A4ProteinHumans
Unknown
Inducer
Details
Prednisolone hemisuccinateCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
Prednisolone phosphateCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inducer
Details
Prednisolone phosphateCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
PrednisoneCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
Prednisone acetateCytochrome P450 3A4ProteinHumans
Unknown
Inducer
Details
Prednisone acetateCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
PrednylideneCytochrome P450 3A4ProteinHumans
No
Substrate
Inducer
Details
PrednylideneCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
RimexoloneCytochrome P450 3A5ProteinHumans
Unknown
Inducer
Details
TriamcinoloneCytochrome P450 3A5ProteinHumans
Unknown
Substrate
Inducer
Details