Cetirizine in horses: pharmacokinetics and pharmacodynamics following repeated oral administration.
The pharmacokinetics of the histamine H(1)-antagonist cetirizine and its effect on histamine-induced cutaneous wheal formation were studied in six healthy horses following repeated oral administration. After three consecutive administrations of cetirizine (0.2 mg/kg body weight, bw) every 12h, the trough plasma concentration of cetirizine was 16+/-4 ng/mL (mean+/-SD) and the wheal formation was inhibited by 45+/-23%. After four additional administrations of cetirizine (0.4 mg/kg bw) every 12 h, the trough plasma concentration was 48+/-15 ng/mL and the wheal formation was inhibited by 68+/-11%. The terminal half-life was about 5.8 h. A pharmacokinetic/pharmacodynamic link model showed that the maximal inhibition of wheal formation was about 95% and the EC(50) about 18 ng/mL. It is concluded that cetirizine in doses of 0.2-0.4 mg/kg bw administered at 12 h intervals exhibits favourable pharmacokinetic and pharmacodynamic properties without causing visible side effects, and the drug may therefore be a useful antihistamine in equine medicine.
Olsén
Lena
L
Division of Pathology, Pharmacology and Toxicology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden. Lena.Olsen@bvf.slu.se
Bondesson
Ulf
U
Broström
Hans
H
Tjälve
Hans
H
Ingvast-Larsson
Carina
C
D000284:Administration, Oral; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D017332:Cetirizine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006736:Horses / Q000097:blood / Q000378:metabolism*
D018926:Anti-Allergic Agents; D017332:Cetirizine