Clarinex - Clinical Pharmacology

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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).

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.

Special Populations:

Geriatric:

In older subjects ( . 65 years old; n= 17) following multiple-dose administra-tion of CLARINEX Tablets, the mean Cmax and AUC values for desloratadine were 20% greater than in younger subjects (< 65 years old). The oral total body clearance (CL/ F) when normalized for body weight was similar between the two age groups. The mean plasma elimination half-life of desloratadine was 33.7 hr in subjects . 65 years old. The pharmacokinetics for 3-hydroxydesloratadine appeared unchanged in older versus younger subjects. These age-related differences are unlikely to be clinically relevant and no dosage adjustment is recom-mended in elderly subjects.