title: Cetirizine in horses: pharmacokinetics and effect of ivermectin pretreatment.
abstract: The pharmacokinetics of the histamine H(1)-antagonist cetirizine and the effects of pretreatment with the antiparasitic macrocyclic lactone ivermectin on the pharmacokinetics of cetirizine were studied in horses. After oral administration of cetirizine at 0.2 mg/kg bw, the mean terminal half-life was 3.4 h (range 2.9-3.7 h) and the maximal plasma concentration 132 ng/mL (101-196 ng/mL). The time to reach maximal plasma concentration was 0.7 h (0.5-0.8 h). Ivermectin (0.2 mg/kg bw) given orally 1.5 h before cetirizine did not affect its pharmacokinetics. However, ivermectin pretreatment 12 h before cetirizine increased the area under the plasma concentration-time curve by 60%. The maximal plasma concentration, terminal half-life and mean residence time also increased significantly following the 12 h pretreatment. Ivermectin is an inhibitor of P-glycoprotein, which is a major drug efflux transporter in cellular membranes at various sites. The elevated plasma levels of cetirizine following the pretreatment with ivermectin may mainly be due to decreased renal secretion, related to inhibition of the P-glycoprotein in the proximal tubular cells of the kidney. The pharmacokinetic properties of cetirizine have characteristics which are suitable for an antihistamine, and this substance may be a useful drug in horses.
authors.affiliation: 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
authors.forename: L
authors.initials: L
authors.lastname: Olsén
authors.forename: C
authors.initials: C
authors.lastname: Ingvast-Larsson
authors.forename: U
authors.initials: U
authors.lastname: Bondesson
authors.forename: H
authors.initials: H
authors.lastname: Broström
authors.forename: H
authors.initials: H
authors.lastname: Tjälve
authors.forename: P
authors.initials: P
authors.lastname: Larsson
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000977:Antiparasitic Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D019540:Area Under Curve; D017332:Cetirizine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006736:Horses / Q000378:metabolism*; D007559:Ivermectin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male
chemical_list: D000977:Antiparasitic Agents; D006634:Histamine H1 Antagonists; D007559:Ivermectin; D017332:Cetirizine