Clenbuterol plasma concentrations after therapeutic administration in fit Standardbred horses: threshold recommendations

Clenbuterol, (RS)-1-(4-amino-3,5-dichlorophenyl)-2-(tert-butylamino)ethan-1-ol, as Ventipulmin is an FDA approved β2 agonist medication for the management of airway obstruction in horses. Administration above the FDA approved doses for clenbuterol produces repartitioning effects, which have led to restrictions on its use in human athletics and Quarter Horse and Thoroughbred racing. Clenbuterol, however has long been used therapeutically at FDA approved doses in Harness racing. The goal of this study was to identify a withdrawal time guideline for its use at FDA approvsed dose levels in Harness racing, where horses may start at seven-day intervals. Eight healthy, moderately fit Standardbred horses (4 mares, 4 geldings, weight 491±40 kg, age 13±2 years) were administered 0.8 μg/kg of clenbuterol as Ventipulmin syrup twice daily (BID) for three days. Blood samples were collected prior to dosing and at 1, 24, 48 and 96 h post administration. Clenbuterol was quantified in all samples using the New York Drug Testing and Research Laboratory ISO-17025 Racing and Medication Testing Consortium (RMTC) accredited quantitative procedure. The lower limit of quantitation of the method was 1.0 pg/ml, and three data points at 96 h post administration were censored. One horse developed diarrhoea and data from this horse was excluded from the overall analysis. Plasma regulatory thresholds were calculated using the 95/95 tolerance method and Gauss Camp Meidell at P=0.05 and P=0.001. Horses were also evaluated for effects of clenbuterol on body composition using body mass and ultrasound measurements of rump fat thickness. There were no effects (P>0.05) of clenbuterol on any of the measures including fat mass and fat free mass and thus no repartitioning effect was observed. The pharmacokinetic data and the 96 h data set support the therapeutic use of clenbuterol in Harness horses at the FDA approved 0.8 μg/kg BID dose for three days and suggest a 41 pg/ml regulatory threshold for a 96 h withdrawal time with a P=0.001 probability of randomly exceeding this regulatory threshold.