Biotransformation of fluticasone: in vitro characterization.

Article Details

Citation

Copy to clipboard

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	Unknown	Substrate Inhibitor Inducer	Details
Fluticasone	Cytochrome P450 3A7	Protein	Humans	Unknown	Substrate	Details
Fluticasone furoate	Cytochrome P450 3A5	Protein	Humans	No	Substrate Inhibitor Inducer	Details
Fluticasone furoate	Cytochrome P450 3A7	Protein	Humans	No	Substrate	Details
Fluticasone propionate	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate Inhibitor	Details
Fluticasone propionate	Cytochrome P450 3A5	Protein	Humans	Unknown	Substrate Inhibitor	Details
Fluticasone propionate	Cytochrome P450 3A7	Protein	Humans	Unknown	Substrate	Details