Metabolism of Loratadine and Further Characterization of Its In Vitro Metabolites

Title: Metabolism of Loratadine and Further Characterization of Its In Vitro Metabolites

Volume: 3 Issue: 3

Author(s): Anima Ghosal, Samir Gupta, Ragu Ramanathan, Yuan Yuan, Xiaowen Lu, Ai Duen (Iris) Su, Narciso Alvarez, Shmuel Zbaida, Swapan K. Chowdhury and Kevin B. Alton

Affiliation:

Keywords: Loratadine, desloratadine, CYP3A4, CYP2D6, CYP2C19

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 AUC24hr 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 (∼70%).

Cite this article as:

Ghosal Anima, Gupta Samir, Ramanathan Ragu, Yuan Yuan, Lu Xiaowen, Su Duen (Iris) Ai, Alvarez Narciso, Zbaida Shmuel, Chowdhury K. Swapan and Alton B. Kevin, Metabolism of Loratadine and Further Characterization of Its In Vitro Metabolites, Drug Metabolism Letters 2009; 3 (3) . https://dx.doi.org/10.2174/187231209789352067