TY - JOUR
T1 - Detection, pharmacokinetics, and selected pharmacodynamic effects of methamphetamine following a single transmucosal and intravenous administration to exercised Thoroughbred horses
AU - Knych, Heather K.
AU - Arthur, Rick M.
AU - Kanarr, Kirsten L.
AU - McKemie, Dan S.
AU - Kass, Philip H.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Methamphetamine is a central and peripheral nervous system stimulant. There is only a single study that describes exposure to and disposition of this compound in horses. The potential for abuse and inadvertent exposure in equine athletes along with the limited data available necessitates further study. The objectives of the current study were to describe drug and metabolite concentrations, develop an analytical method that could be used to regulate its use, and describe selected pharmacodynamic effects. In phase 1, six horses were randomized into three transmucosal dose groups (n = 2/group; 0.5, 1.0 or 10 mg). In phase 2, horses received a single 10 mg intravenous dose. In phase 3, the effects of urinary pH on elimination were studied. Blood and urine samples were collected for up to 72 hours post drug administration. Concentrations of methamphetamine were measured using liquid chromatography–tandem mass spectrometry. Methamphetamine was below the limit of detection (LOD) in blood by 2, 4, and 18 hours following transmucosal administration of 0.5, 1, and 10 mg, respectively. Following intravenous administration, methamphetamine fell below the LOD between 12 and 18 hours. Following urinary acidification, methamphetamine fell below the limit of quantitation (LOQ) by 12 hours. In urine, methamphetamine was no longer detected at 48, 48, and 72 hours in the 0.5, 1, and 10 mg transmucosal groups and 18 hours in the intravenous group. Increased urinary pH resulted in urinary concentrations of methamphetamine falling below detectable levels by 48 hours post transmucosal administration. While the number of animals was small, behavioral, stimulatory, and cardiac effects were minimal.
AB - Methamphetamine is a central and peripheral nervous system stimulant. There is only a single study that describes exposure to and disposition of this compound in horses. The potential for abuse and inadvertent exposure in equine athletes along with the limited data available necessitates further study. The objectives of the current study were to describe drug and metabolite concentrations, develop an analytical method that could be used to regulate its use, and describe selected pharmacodynamic effects. In phase 1, six horses were randomized into three transmucosal dose groups (n = 2/group; 0.5, 1.0 or 10 mg). In phase 2, horses received a single 10 mg intravenous dose. In phase 3, the effects of urinary pH on elimination were studied. Blood and urine samples were collected for up to 72 hours post drug administration. Concentrations of methamphetamine were measured using liquid chromatography–tandem mass spectrometry. Methamphetamine was below the limit of detection (LOD) in blood by 2, 4, and 18 hours following transmucosal administration of 0.5, 1, and 10 mg, respectively. Following intravenous administration, methamphetamine fell below the LOD between 12 and 18 hours. Following urinary acidification, methamphetamine fell below the limit of quantitation (LOQ) by 12 hours. In urine, methamphetamine was no longer detected at 48, 48, and 72 hours in the 0.5, 1, and 10 mg transmucosal groups and 18 hours in the intravenous group. Increased urinary pH resulted in urinary concentrations of methamphetamine falling below detectable levels by 48 hours post transmucosal administration. While the number of animals was small, behavioral, stimulatory, and cardiac effects were minimal.
KW - horse
KW - horse racing
KW - mass spectrometry
KW - methampetamine
KW - stimulant
UR - http://www.scopus.com/inward/record.url?scp=85072905181&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072905181&partnerID=8YFLogxK
U2 - 10.1002/dta.2661
DO - 10.1002/dta.2661
M3 - Article
C2 - 31218824
AN - SCOPUS:85072905181
VL - 11
SP - 1431
EP - 1443
JO - Drug Testing and Analysis
JF - Drug Testing and Analysis
SN - 1942-7603
IS - 9
ER -