title: Fexofenadine in horses: pharmacokinetics, pharmacodynamics and effect of ivermectin pretreatment.
abstract: The pharmacokinetics and the effects on inhibition of histamine-induced cutaneous wheal formation of the histamine H1-antagonist fexofenadine were studied in horse. The effect of ivermectin pretreatment on the pharmacokinetics of fexofenadine was also examined. After intravenous infusion of fexofenadine at 0.7 mg/kg bw the mean terminal half-life was 2.4 h (range: 2.0-2.7 h), the apparent volume of distribution 0.8 L/kg (0.5-0.9 L/kg), and the total body clearance 0.8 L/h/kg (0.6-1.2 L/h/kg). After oral administration of fexofenadine at 10 mg/kg bw bioavailability was 2.6% (1.9-2.9%). Ivermectin pretreatment (0.2 mg/kg, p.o.) 12 h before oral fexofenadine decreased the bioavailability to 1.5% (1.4-2.1%). In addition, the area under the plasma concentration-time curve decreased 27%. Ivermectin did not affect the pharmacokinetics of i.v. administered fexofenadine. Ivermectin may influence fexofenadine absorption by interfering in intestinal efflux and influx pumps, such as P-glycoprotein and the organic anion transport polypeptide family. Oral and i.v. fexofenadine significantly decreased histamine-induced wheal formation, with a maximal duration of 6 h. A pharmacokinetic/pharmacodynamic link model indicated that fexofenadine in horse has antihistaminic effects at low plasma concentrations (EC50 = 16 ng/mL). However, oral treatments of horses with fexofenadine may not be suitable due to the low bioavailability.
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: P
authors.initials: P
authors.lastname: Larsson
authors.forename: H
authors.initials: H
authors.lastname: Broström
authors.forename: U
authors.initials: U
authors.lastname: Bondesson
authors.forename: M
authors.initials: M
authors.lastname: Sundqvist
authors.forename: H
authors.initials: H
authors.lastname: Tjälve
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006634:Histamine H1 Antagonists / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D006736:Horses; D007559:Ivermectin / Q000494:pharmacology*; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000977:Antiparasitic Agents; D006634:Histamine H1 Antagonists; D007559:Ivermectin; D016593:Terfenadine; C093230:fexofenadine