Metabolism of loratadine and further characterization of its in vitro metabolites.
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Ghosal A, Gupta S, Ramanathan R, Yuan Y, Lu X, Su AD, Alvarez N, Zbaida S, Chowdhury SK, Alton KB
Metabolism of loratadine and further characterization of its in vitro metabolites.
Drug Metab Lett. 2009 Aug;3(3):162-70. Epub 2009 Aug 1.
- PubMed ID
- 19702548 [ View in PubMed]
- Abstract
The present study demonstrated that in addition to CYP3A4 and CYP2D6, the metabolism of loratadine is also catalyzed by CYP1A1, CYP2C19, and to a lesser extent by CYP1A2, CYP2B6, CYP2C8, CYP2C9 and CYP3A5. The biotransformation of loratadine was associated with the formation of desloratadine (DL) and further hydroxylation of both DL and the parent drug (loratadine). Based on the inhibition and correlation studies contribution of CYP2C19 in the formation of the major circulating metabolite DL seems to be minor. Reported clinical results suggest that the steady state mean (%CV) plasma Cmax and AUC(24hr) of loratadine were 4.73 ng/ml (119%) and 24.1 ng.hr/ml (157%), respectively, after dosing with 10 mg loratadine tablets for 10 days. High inter-subject variability in loratadine steady-state data is probably due to the phenotypical characteristics of CYP2D6, CYP2C19, and CYP3A4. The relative abundance of CYP3A4 in the human liver exceeds that of CYP2C19 and CYP2D6 and therefore the contribution of CYP3A4 in the metabolism of loratadine should be major (approximately 70%).
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Loratadine Cytochrome P450 1A1 Protein Humans NoSubstrateDetails Loratadine Cytochrome P450 1A2 Protein Humans UnknownSubstrateDetails Loratadine Cytochrome P450 2B6 Protein Humans UnknownSubstrateDetails Loratadine Cytochrome P450 2C19 Protein Humans NoSubstrateInhibitorDetails Loratadine Cytochrome P450 2C9 Protein Humans UnknownSubstrateDetails Loratadine Cytochrome P450 3A5 Protein Humans UnknownSubstrateDetails