Desloratadine Demonstrates Dose Proportionality in Healthy Adults After Single Doses

Abstract

Objective: To evaluate the dose proportionality and linearity and pharmacokinetic profile of desloratadine after single oral doses over the range of 5 to 20mg.

Design: Single centre, randomised, open-label, 4-way crossover study in which healthy adults received single doses of desloratadine (5, 7.5, 10 and 20mg) in 4 different treatment periods. Desloratadine was administered each morning after a 10-hour fast. A washout period of at least 14 days separated each dose. Plasma concentrations were measured prior to each treatment and over the 168 hours after drug administration to determine the area under the plasma concentration-time curve (AUC) and maximum observed plasma concentration (C_max).

Participants: 20 healthy male volunteers (3 White, 17 Black) ranging in age from 19 to 45 (mean 37) years and weighing 54 to 91 (mean 75) kg were enrolled and completed this study.

Main outcome measures: The primary parameter to assess dose proportionality and linearity was AUC from time zero to final concentration time point (AUCs).

Results: The C_max for all doses was observed approximately 4 hours after administration, revealing no dose-related differences in absorption rate. The half-life (t1/2) ranged from 21.2 to 24.1 hours. C_max and AUC_s increased in a doseproportional manner over a dose range of 5 to 20mg. Although the recommended clinical dose is 5mg, doses up to 20mg were well tolerated.

Conclusion: In this study, single doses of desloratadine as high as 4 times the recommended clinical dose of 5mg were well tolerated. The C_max and AUCs for doses of 5 to 20mg increased in a dose-proportional manner.