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Metabolism Desloratadine (a major metabolite of loratadine) is extensively metabolized to 3-hydroxydeslor-atadine, an active metabolite, which is subsequently glucuronidated. The enzyme( s) responsible for the formation of 3-hydroxydesloratadine have not been identified. Data from clinical trials indicate that a subset of the general patient population has a decreased ability to form 3-hydroxydesloratadine, and are slow metabo-lizers of desloratadine. In pharmacokinetic studies (n= 1087), approximately 7% of subjects were slow metabo-lizers of desloratadine (defined as a subject with an AUC ratio of 3-hydroxydesloratadine to desloratadine less than 0.1, or a subject with a desloratadine half-life exceeding 50 hours). The frequency of slow metabolizers is higher in Blacks (approximately 20% of Blacks were slow metabolizers in pharmacokinetic studies, n= 276). Text Continues Below
The median exposure (AUC) to desloratadine in the slow metabolizers was approximately 6-fold greater than the subjects who are not slow metabolizers. Subjects who are slow metabolizers of desloratadine cannot be prospectively identified and will be exposed to higher levels of desloratadine following dosing with the recom-mended dose of desloratadine. Although not seen in these pharmacokinetic studies, patients who are slow metabolizers may be more susceptible to dose-related adverse events. Elimination: The mean elimination half-life of desloratadine was 27 hours. Cmax and AUC values increased in a dose proportional manner following single oral doses between 5 and 20 mg. The degree of accumulation after 14 days of dosing was consistent with the half-life and dosing frequency. A human mass balance study docu-mented a recovery of approximately 87% of the 14 C-desloratadine dose, which was equally distributed in urine and feces as metabolic products. Analysis of plasma 3-hydroxydesloratadine showed similar Tmax and half-life values compared to desloratadine. Page: << Prev | 1 | 2 | 3 | 4 | Next >>
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