Biotransformation of fluticasone: in vitro characterization.
Article Details
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Pearce RE, Leeder JS, Kearns GL
Biotransformation of fluticasone: in vitro characterization.
Drug Metab Dispos. 2006 Jun;34(6):1035-40. Epub 2006 Mar 24.
- PubMed ID
- 16565171 [ View in PubMed]
- Abstract
Fluticasone propionate (FTP) is a synthetic trifluorinated glucocorticoid with potent anti-inflammatory action that is commonly used in patients with asthma. After oral or intranasal administration, FTP undergoes rapid hepatic biotransformation; the principal metabolite formed is a 17beta-carboxylic acid derivative (M1). M1 formation has been attributed largely to cytochrome P450 3A4 (CYP3A4); however, there are no published data that confirm this assertion. Hence, in vitro studies were conducted to determine the role that human P450s play in the metabolism of FTP. Consistent with in vivo data, human liver microsomes catalyzed the formation of a single metabolite (M1) at substrate concentrations
0.95) with CYP3A4/5 activities in a panel of human liver microsomes (n = 14) and was markedly impaired by the CYP3A inhibitor ketoconazole (>94%) but not by inhibitors of other P450 enzymes (
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Fluticasone Cytochrome P450 3A5 Protein Humans UnknownSubstrateInhibitorInducerDetails Fluticasone Cytochrome P450 3A7 Protein Humans UnknownSubstrateDetails Fluticasone furoate Cytochrome P450 3A5 Protein Humans NoSubstrateInhibitorInducerDetails Fluticasone furoate Cytochrome P450 3A7 Protein Humans NoSubstrateDetails Fluticasone propionate Cytochrome P450 3A4 Protein Humans UnknownSubstrateInhibitorDetails Fluticasone propionate Cytochrome P450 3A5 Protein Humans UnknownSubstrateInhibitorDetails Fluticasone propionate Cytochrome P450 3A7 Protein Humans UnknownSubstrateDetails