Pharmacokinetics and effects of aminorex in horses.
OBJECTIVE
To investigate the pharmacokinetics and behavioral effects of aminorex administered IV and PO in horses.


METHODS
7 Thoroughbreds.


METHODS
In a cross-over design, aminorex (0.03 mg/kg) was administered IV or PO. Plasma and urinary aminorex concentrations were determined via liquid chromatography- mass spectrometry.


RESULTS
Decrease of aminorex from plasma following IV administration was described by a 3-compartment pharmacokinetic model. Median (range) values of alpha, beta, and gamma half-lives were 0.04 (0.01 to 0.28), 2.30 (1.23 to 3.09), and 18.82 (8.13 to 46.64) hours, respectively. Total body and renal clearance, the area under the plasma time curve, and initial volume of distribution were 37.26 (28.61 to 56.24) mL x min/kg, 1.25 (0.85 to 2.05) mL x min/kg, 13.39 (8.82 to 17.37) ng x h/mL, and 1.44 (0.10 to 3.64) L/kg, respectively. Oral administration was described by a 2-compartment model with first-order absorption, elimination from the central compartment, and distribution into peripheral compartments. The absorption half-life was 0.29 (0.12 to 1.07) hours, whereas the beta and gamma elimination phases were 1.93 (1.01 to 3.17) and 23.57 (15.16 to 47.45) hours, respectively. The area under the curve for PO administration was 10.38 (4.85 to 13.40) ng.h/mL and the fractional absorption was 81.8% (33.8% to 86.9%).


CONCLUSIONS
Aminorex administered IV had a large volume of distribution, initial rapid decrease, and an extended terminal elimination. Following PO administration, there was rapid absorption, rapid initial decrease, and an extended terminal elimination. At a dose of 0.03 mg/kg, the only effects detected were transient and central in origin and were observed only following IV administration.
Soma
Lawrence R
LR
New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348, USA.
Rudy
Jeffrey A
JA
Uboh
Cornelius E
CE
Xu
Fran
F
Snapp
Heidi M
HM
D000284:Administration, Oral; D000635:Aminorex / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine; D000818:Animals; D019540:Area Under Curve; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006736:Horses / Q000378:metabolism*; D007262:Infusions, Intravenous; D008297:Male; D011897:Random Allocation
D000697:Central Nervous System Stimulants; D000635:Aminorex