Pharmacokinetics of the new antiasthma and antiallergy drug, azelastine, in pediatric and adult beagle dogs.
The plasma concentrations and relative bioavailability of azelastine hydrochloride (AZ) and its desmethyl metabolite (DAZ) after a single and 10 once-a-day oral doses of 2.5 mg kg-1 AZ were determined in adult male and female and pediatric male and female beagle dogs. The pediatric and adult dogs were 4-6 weeks and 1-2 years of age, respectively. An analysis of variance (ANOVA) was performed on the bioavailability parameters among all groups and between the first and last doses. No statistically significant (p < 0.05) sex-related differences in the bioavailability parameters were observed. The peak concentration (Cmax) of AZ, especially after the first dose, was significantly higher in pediatric dogs than that in adult dogs, whereas following the multiple AZ administrations, the bioavailability parameters for the last dose were similar in the two age groups. The apparent volume of distribution (Vss) of AZ suggested that the drug was extensively distributed into tissue in adult as well as in pediatric dogs. The Vss was considerably smaller in pediatric dogs, which may explain the higher Cmax in this age group. The bioavailability of the metabolite in adult dogs after multiple administration of AZ was higher than that in pediatric dogs. Although some differences in the parameters among the groups are statistically significant, they do not appear to have any biological significance. Therefore, similar AZ dosages may be required in pediatric and in adult populations to achieve optimum therapeutic drug levels.
Adusumalli
V E
VE
Wallace Laboratories, Division of Carter-Wallace, Inc., Cranbury, NJ 08512.
Wichmann
J K
JK
Wong
K K
KK
Kucharczyk
N
N
Sofia
R D
RD
D000818:Animals; D001682:Biological Availability; D001993:Bronchodilator Agents / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005260:Female; D006207:Half-Life; D006634:Histamine H1 Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D010793:Phthalazines / Q000097:blood / Q000493:pharmacokinetics*
D001993:Bronchodilator Agents; D006634:Histamine H1 Antagonists; D010793:Phthalazines; C054114:desmethylazelastine; C020976:azelastine