Knych, Heather K., Stanley, Scott D., McKemie, Dan S., Arthur, Rick M., Bondesson, Ulf, Hedeland, Mikael, Thevis, Mario and Kass, Philip H. (2017). Pharmacokinetics and pharmacodynamics of meldonium in exercised thoroughbred horses. Drug Test. Anal., 9 (9). S. 1392 - 1400. HOBOKEN: WILEY. ISSN 1942-7611

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Abstract

Although developed as a therapeutic medication, meldonium has found widespread use in human sports and was recently added to the World Anti-Doping Agency's list of prohibited substances. Its reported abuse potential in human sports has led to concern by regulatory authorities about the possible misuse of meldonium in equine athletics. The potential abuse in equine athletes along with the limited data available regarding the pharmacokinetics and pharmacodynamics of meldonium in horses necessitates further study. Eight exercised adult thoroughbred horses received a single oral dose of 3.5, 7.1, 14.3 or 21.4 mg/kg of meldonium. Blood and urine samples were collected and analyzed using liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were determined using non-compartmental analysis. Maximum serum concentrations ranged from 440.2 to 1147 ng/mL and the elimination half-life from 422 to 647.8 h. Serum concentrations were below the limit of quantitation by days 4, 7, 12 and 12 for doses of 3.5, 7.1, 14.3 and 21.4 mg/kg, respectively. Urine concentrations were below the limit of detection by day 44 following administration of 3.5 mg/kg and day 51 for all other dose groups. No adverse effects were observed following meldonium administration. While the group numbers were small, changes in heart rate were observed in the 3.5 mg/kg dose group (n = 1). Glucose concentrations changed significantly in all dose groups studied (n = 2 per dose group). Similar to that reported for humans, the detection time of meldonium in biological samples collected from horses is prolonged, which should allow for satisfactory regulation in performance horses. Copyright (C) 2017 John Wiley & Sons, Ltd.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Knych, Heather K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stanley, Scott D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McKemie, Dan S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arthur, Rick M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bondesson, UlfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hedeland, MikaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thevis, MarioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kass, Philip H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-218635
DOI: 10.1002/dta.2214
Journal or Publication Title: Drug Test. Anal.
Volume: 9
Number: 9
Page Range: S. 1392 - 1400
Date: 2017
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1942-7611
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MILDRONATE; RATS; CARNITINE; MET-88; VOLUNTEERS; SINGLE; HEARTMultiple languages
Biochemical Research Methods; Chemistry, Analytical; Pharmacology & PharmacyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/21863

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