Further Characterization of the Metabolism of Desloratadine and Its Cytochrome P450 and UDP-glucuronosyltransferase Inhibition Potential: Identification of Desloratadine as a Relatively Selective UGT2B10 Inhibitor

Desloratadine (Clarinex), the major active metabolite of loratadine (Claritin), is a nonsedating antihistamine used for the treatment of seasonal allergies and hives. Previously we reported that the formation of 3-hydroxydesloratadine, the major human metabolite of desloratadine, involves three sequ...

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Published in:Drug metabolism and disposition 2015-09, Vol.43 (9), p.1294-1302
Main Authors: Kazmi, Faraz, Yerino, Phyllis, Barbara, Joanna E., Parkinson, Andrew
Format: Article
Language:English
Subjects:
Cytochrome P-450 Enzyme System - drug effects
Enzyme Inhibitors - pharmacokinetics
Enzyme Inhibitors - pharmacology
Glucuronosyltransferase - antagonists & inhibitors
Histamine H1 Antagonists, Non-Sedating - pharmacokinetics
Histamine H1 Antagonists, Non-Sedating - pharmacology
Humans
Loratadine - analogs & derivatives
Loratadine - pharmacokinetics
Loratadine - pharmacology
Microsomes, Liver - drug effects
Microsomes, Liver - enzymology
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Summary:Desloratadine (Clarinex), the major active metabolite of loratadine (Claritin), is a nonsedating antihistamine used for the treatment of seasonal allergies and hives. Previously we reported that the formation of 3-hydroxydesloratadine, the major human metabolite of desloratadine, involves three sequential reactions, namely N-glucuronidation by UGT2B10 followed by 3-hydroxylation by CYP2C8 followed by deconjugation (rapid, nonenzymatic hydrolysis of the N-glucuronide). In this study we assessed the perpetrator potential of desloratadine based on in vitro studies of its inhibitory effects on cytochrome P450 and UDP-glucuronosyltransferase (UGT) enzymes in human liver microsomes (HLM). Desloratadine (10 µM) caused no inhibition (
ISSN:0090-9556
1521-009X
DOI:10.1124/dmd.115.065011