Desloratadine demonstrates dose proportionality in healthy adults after single doses.
OBJECTIVE
To evaluate the dose proportionality and linearity and pharmacokinetic profile of desloratadine after single oral doses over the range of 5 to 20mg.


METHODS
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)).


METHODS
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.


METHODS
The primary parameter to assess dose proportionality and linearity was AUC from time zero to final concentration time point (AUC(S)).


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 (t((1/2))) ranged from 21.2 to 24.1 hours. C(max) and AUC(S) increased in a dose-proportional manner over a dose range of 5 to 20mg. Although the recommended clinical dose is 5mg, doses up to 20mg were well tolerated.


CONCLUSIONS
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 AUC(S) for doses of 5 to 20mg increased in a dose-proportional manner.
Gupta
Samir
S
Schering-Plough Research Institute, Kenilworth, New Jersey 07033-0539, USA.
Banfield
Christopher
C
Affrime
Melton
M
Marco
Aliceann
A
Cayen
Mitchell
M
Herron
Jerry
J
Padhi
Desmond
D
D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D017336:Loratadine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged
D006634:Histamine H1 Antagonists; D017336:Loratadine; C121345:desloratadine