Effect of an endurance-like exercise on the disposition and detection time of phenylbutazone and dexamethasone in the horse: application to medication control.
BACKGROUND
Equine antidoping rules were established to prevent a horse's performance being altered after the administration of prohibited substances, including approved drugs used for legitimate treatment. Veterinarians have to advise owners or trainers on appropriate withholding times to guarantee that their horses may safely compete after drug administration. In order to propose tailored withdrawal times, several horse organisations released detection time (DT) values, for the main veterinary drugs used in horses. One of the possible limits to the information provided by published DTs in horses is the fact that they are determined from classic pharmacokinetic studies performed at rest under laboratory conditions. In field conditions, training and exercise programmes may have an influence on drug elimination.


METHODS
Dexamethasone (DMX) and phenylbutazone (PBZ) have been quantified in plasma and urine after solid phase extraction. The kinetic disposition of DXM (8 microg/kg) and PBZ (8 mg/kg) administered by i.v. route in 8 horses, was investigated in rest conditions and during a standardised 3 h test exercise according to a cross-over design.


OBJECTIVE
The aim of the present study was to compare the kinetic disposition of 2 test drugs, DMX and PBZ in rest vs. exercising conditions.


RESULTS
It was shown in 8 horses that a sustained 3 h of mild exercise slightly decreased the plasma clearance of both drugs (about 25% for DXM and 37% for PBZ) and this is mainly explained by the significant decrease of the corresponding hepatic clearance. In addition, as the volume of distribution was correlatively decreased, the plasma terminal half-life, which is a hybrid parameter of plasma clearance and volume of distribution, remains unchanged overall.


CONCLUSIONS
Establishing DTs or withdrawal times (WTs) are relevant as plasma and urine half-lives, but not clearance, are the main determinants of DT length. Veterinarians may realistically decide upon a WT for a legitimate drug based on the corresponding DT obtained under resting conditions providing this drug has a low hepatic extraction ratio and a safety margin is added to allow for all possible sources of variability.
Authie
E C
EC
UMR181 Physiopathologie et Toxicologie Expérimentales INRA, ENVT-Ecole Nationale Vétérinaire de Toulouse, 23 chemin des Capelles-31076 Toulouse cedex 3, France.
Garcia
P
P
Popot
M A
MA
Toutain
P L
PL
Doucet
M
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D001800:Blood Specimen Collection; D003907:Dexamethasone / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006736:Horses / Q000378:metabolism*; D008297:Male; D010653:Phenylbutazone / Q000097:blood / Q000493:pharmacokinetics*; D010805:Physical Conditioning, Animal
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; D010653:Phenylbutazone