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Cetirizine per os: exposure and antihistamine effect in the dog
Swedish Univ Agr Sci, Div Pharmacol & Toxicol, Dept Biomed & Vet Publ Hlth, POB 7028, S-75007 Uppsala, Sweden.ORCID iD: 0000-0001-7480-9935
Swedish Univ Agr Sci, Div Pharmacol & Toxicol, Dept Biomed & Vet Publ Hlth, POB 7028, S-75007 Uppsala, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry. Natl Vet Inst, Dept Chem Environm & Feed Hyg, Uppsala, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry. Natl Vet Inst, Dept Chem Environm & Feed Hyg, Uppsala, Sweden.ORCID iD: 0000-0001-8962-2815
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2018 (English)In: Acta Veterinaria Scandinavica, ISSN 1751-0147, E-ISSN 1751-0147, Vol. 60, article id 77Article in journal (Refereed) Published
Abstract [en]

BackgroundCetirizine is an antihistamine used in dogs, but plasma concentrations in relation to effect after oral administration are not well studied. This study investigated cetirizine exposure and the plasma cetirizine concentration-antihistamine response relation in the dog following oral administration of cetirizine.ResultsEight Beagle dogs were included in a cross-over study consisting of two treatments. In treatment one, cetirizine 2-4mg/kg was administered per os once daily for 3days. The other treatment served as a control. Wheal diameter induced by intra-dermal histamine injections served as response-biomarker. Cetirizine plasma concentration was quantified by UHPLC-MS/MS. Median (range) cetirizine plasma terminal half-life was 10h (7.9-16.5). Cetirizine significantly inhibited wheal formation compared with the premedication baseline. Maximum inhibition of wheal formation after treatment with cetirizine per os was 100% compared with premedication wheal diameter. The median (range) IC50-value for reduction in wheal area was 0.33 mu g/mL (0.07-0.45). The median (range) value for the sigmoidicity factor was 1.8 (0.8-3.5). A behavioral study was also conducted and revealed no adverse effects, such as sedation.ConclusionThe results indicate that a once-daily dosing regimen of 2-4mg/kg cetirizine per os clearly provides a sufficient antihistamine effect. Based on this experimental protocol, cetirizine may be an option to treat histamine-mediated inflammation in the dog based on this experimental protocol but additional clinical studies are required.

Place, publisher, year, edition, pages
BMC , 2018. Vol. 60, article id 77
Keywords [en]
Anti-inflammatory, Efficacy, Pharmacodynamics, Pharmacokinetics, Potency
National Category
Medical Bioscience
Identifiers
URN: urn:nbn:se:uu:diva-372332DOI: 10.1186/s13028-018-0431-3ISI: 000451251500001PubMedID: 30477556OAI: oai:DiVA.org:uu-372332DiVA, id: diva2:1276351
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-01-08Bibliographically approved

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Bondesson, UlfHedeland, Mikael

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