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.
Publication Date: 2006-03-07 PubMed ID: 16515667DOI: 10.1111/j.1365-2885.2006.00724.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research explores the pharmacokinetics and pharmacodynamics of fexofenadine, a histamine H1-antagonist, in horses. The study also examines the impact of ivermectin pretreatment on the pharmacokinetics of fexofenadine. Results highlight a low bioavailability following oral administration, indicating that fexofenadine may not be suitable for oral treatments in horses.
Fexofenadine Pharmacokinetics in Horses
- This study investigated the pharmacokinetics, or bodily absorption and distribution, of fexofenadine in horses.
- Fexofenadine, after intravenous infusion at a dose of 0.7 mg/kg body weight, had an average terminal half-life of 2.4 hours (range: 2-2.7 hours), an apparent volume of distribution of 0.8 L/kg (0.5-0.9 L/kg), and a total body clearance rate of 0.8 L/h/kg (0.6-1.2 L/h/kg).
Oral Administration and Bioavailability
- Fexofenadine showed low bioavailability of 2.6% (1.9-2.9%) after orally administered at a dose of 10 mg/kg body weight.
- Low bioavailability means a smaller proportion of the administered medication was absorbed and available for use in the body.
Effect of Ivermectin Pretreatment
- The research also explored the effect of ivermectin, an anti-parasite drug, on the pharmacokinetics of fexofenadine when given as a pretreatment.
- Ivermectin pretreatment reduced the bioavailability of orally administered fexofenadine to 1.5% (1.4-2.1%), indicating interference with fexofenadine absorption.
- Ivermectin, however, had no impact on the pharmacokinetics of intravenous fexofenadine.
Fexofenadine Pharmacodynamics and Histamine-induced Wheal Formation
- Fexofenadine showed significant inhibition of histamine-induced wheal (hives) formation after both oral and intravenous administration, with a duration of effect up to 6 hours.
- A pharmacokinetic/pharmacodynamic link model revealed the antihistamine effects of fexofenadine even at low plasma concentrations (EC50 = 16 ng/mL).
Treatment Implications
- Despite its effectiveness in decreasing histamine-induced wheal formation, fexofenadine’s low oral bioavailability makes it less suitable for oral treatments in horses.
- The data suggest fexofenadine may be more appropriately administered intravenously.
Cite This Article
APA
Olsén L, Ingvast-Larsson C, Larsson P, Broström H, Bondesson U, Sundqvist M, Tjälve H.
(2006).
Fexofenadine in horses: pharmacokinetics, pharmacodynamics and effect of ivermectin pretreatment.
J Vet Pharmacol Ther, 29(2), 129-135.
https://doi.org/10.1111/j.1365-2885.2006.00724.x Publication
Researcher Affiliations
- 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
MeSH Terms
- Animals
- Antiparasitic Agents / pharmacology
- Area Under Curve
- Biological Availability
- Drug Interactions
- Female
- Half-Life
- Histamine H1 Antagonists / blood
- Histamine H1 Antagonists / pharmacokinetics
- Histamine H1 Antagonists / pharmacology
- Horses
- Ivermectin / pharmacology
- Terfenadine / analogs & derivatives
- Terfenadine / blood
- Terfenadine / pharmacokinetics
- Terfenadine / pharmacology
Citations
This article has been cited 6 times.- Ikeda Y, Kuroda T, Mita H, Tamura N, Ohta M. Comparing the effectiveness of four antihistamines with olopatadine in healthy Thoroughbred horses. J Vet Med Sci 2025 Feb 4;87(2):171-174.
- Rosa B. Equine Drug Transporters: A Mini-Review and Veterinary Perspective. Pharmaceutics 2020 Nov 8;12(11).
- Kigen G, Edwards G. Drug-transporter mediated interactions between anthelminthic and antiretroviral drugs across the Caco-2 cell monolayers. BMC Pharmacol Toxicol 2017 May 4;18(1):20.
- El-Kommos ME, El-Gizawy SM, Atia NN, Hosny NM. Determination of Some Non-sedating Antihistamines via Their Native Fluorescence and Derivation of Some Quantitative Fluorescence Intensity - Structure Relationships. J Fluoresc 2015 Nov;25(6):1695-709.
- Lon HK, Liu D, Jusko WJ. Pharmacokinetic/pharmacodynamic modeling in inflammation. Crit Rev Biomed Eng 2012;40(4):295-312.
- Gundogdu E, Mangas-Sanjuan V, Gonzalez-Alvarez I, Bermejo M, Karasulu E. In vitro-in situ permeability and dissolution of fexofenadine with kinetic modeling in the presence of sodium dodecyl sulfate. Eur J Drug Metab Pharmacokinet 2012 Mar;37(1):65-75.
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