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Drugs in horses

pharmacokinetics and pharmacodynamics

Olsén, Lena (2007). Drugs in horses. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae, 1652-6880 ; 2007:37
ISBN 978-91-576-7336-7
[Doctoral thesis]

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Abstract

In this thesis the fate and effect of some drugs have been examined in horses. Studies have also been performed to explore some factors which may affect the pharmacokinetics and the pharmacodynamics of drugs in horses. Investigations on the drug metabolising enzyme cytochrome P450 3A (CYP3A) in the intestines of horses showed high gene expression and metabolic activity in the proximal parts of the intestines. The results indicate that CYP3A in the intestines of horse plays a major role in the first-pass metabolism of drugs which are substrates for CYP3A. There is a need for an antihistamine for oral therapy of horses. The oral bioavailability of the antihistamine fexofenadine was found to be low, and this drug is therefore unsuitable for oral use in horses. In contrast oral administration of the antihistamine cetirizine resulted in a sufficient uptake. This drug was also found to have a potent antihistaminic effect in horses. Cetirizine may therefore be a suitable antihistamine in equine medicine. The passage of antihistamines, such as fexofenadine and cetirizine, as well as several other xenobiotics, over cell-membranes in various tissues is partly regulated by transport proteins. Studies in this thesis showed that pre-treatment of horses with the antiparasitic agent ivermectin affects the oral bioavailability of fexofenadine and cetirizine. The effect of ivermectin is probably related to interference in the function of the transport proteins. Acute adverse reactions may occur following treatments of horses with procaine benzylpenicillin or potassium or sodium benzylpenicillin. Analysis of adverse reactions reported in 59 horses indicates that allergy may underlie a few of the cases. However, most reactions may be due to toxic effects of procaine. Several mechanisms may contribute to the procaine toxicity. It was shown that the ability of plasma esterases to hydrolyze procaine to non-toxic metabolites was lower in reacting horses compared to non-reacting control horses. Low plasma esterase activity may increase the likelihood for procaine toxicity and constitute one risk factor.

Authors/Creators:Olsén, Lena
Title:Drugs in horses
Subtitle:pharmacokinetics and pharmacodynamics
Year of publishing :April 2007
Volume:2007:37
Number of Pages:56
Papers/manuscripts:
NumberReferences
ALLI. Tydén, E., Olsén, L., Tallkvist, J., Larsson; P., Tjälve, H. (2004) CYP3A in horse intestines. Toxicology and Applied Pharmacology. 201: 112-119. II. 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 pre-treatment. Journal of Veterinary Pharmacology and Therapeutics. 29:129-135. III. Olsén, L., Ingvast-Larsson, C., Broström, H., Bondesson, U., Tjälve, H., Larsson, P. (2007). Cetirizine in horses: pharmacokinetics and effect of ivermectin pre-treatment. Journal of Veterinary Pharmacology and Therapeutics. Accepted for publication. IV. Olsén, L., Bondesson, U., Broström, H., Tjälve, H., Ingvast-Larsson, C. (2007). Cetirizine in horses: pharmacokinetics and pharmacodynamics following repeated oral administrations. The Veterinary Journal. Accepted for publication. V. Olsén, L., Ingvast-Larsson, C., Broström, H., Larsson, P., Tjälve, H. (2007). Clinical signs and etiology of adverse reactions to procaine benzylpenicillin and sodium/potassium benzylpenicillin in horses. Journal of Veterinary Pharmacology and Therapeutics. Accepted for publication.
Place of Publication:Uppsala
ISBN for printed version:978-91-576-7336-7
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Full Text Status:Public
Agrovoc terms:horses, intestines, medicinal properties, pharmacology, enzymes, antihistaminics, drugs, penicillins, procaine, side effects, drug allergies
Keywords:Keywords: horse, CYP3A, intestine, pharmacokinetics, pharmacodynamics, antihistamine, cetirizine, fexofenadine, ivermectin, drug interactions, adverse reaction, penicillin, procaine, plasma esterase
URN:NBN:urn:nbn:se:slu:epsilon-1549
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-1549
ID Code:1389
Department:(VH) > Dept. of Biomedical Sciences and Veterinary Public Health
Deposited By: Lena Olsén
Deposited On:18 Apr 2007 00:00
Metadata Last Modified:02 Dec 2014 10:11

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