title: Detection, pharmacokinetics and cardiac effects following administration of clenbuterol to exercised horses.
abstract: BACKGROUND
  The use of clenbuterol in performance horses necessitates the establishment of appropriate withdrawal times.
  
  
  OBJECTIVE
  To describe plasma and urine concentrations of clenbuterol following administration of 2 commonly used dosing regimens to racing fit Thoroughbreds.
  
  
  METHODS
  Experimental.
  
  
  METHODS
  Twenty-two horses received an oral dose of 0.8 μg/kg bwt of clenbuterol twice daily for 30 days. A second group of 6 horses received clenbuterol according to the escalating dose protocol on the manufacturer's label. Blood and urine samples were collected prior to, throughout and at various times up to 35 days post administration of the final dose. Drug concentrations were measured using liquid chromatography-mass spectrometry, and plasma data were analysed using noncompartmental analysis. Behavioural and physiological effects were monitored and heart rate was recorded throughout the course of the study.
  
  
  RESULTS
  Clenbuterol plasma concentrations were below the limit of quantification (10 pg/ml) of the assay by Day 4 in all horses receiving the chronic low-dose regimen and by Day 7 in 5 of 6 horses receiving the escalating dosing protocol. Urine clenbuterol concentrations fell below the limit of quantification of the assay between Days 21 and 28 in all 22 horses in the low-dose group and in 5 of 6 of the horses in the escalating dose group. Muscle fasciculations, sweating and transient increases in heart rate were noted in a small number of horses following clenbuterol administration, but tolerance to these effects occurred rapidly.
  
  
  CONCLUSIONS
  Establishment of appropriate withdrawal times for specific racing jurisdictions depends upon the threshold adopted by that specific jurisdiction. This study extends previous studies describing the pharmacokinetics of clenbuterol and describes plasma and urine concentrations following administration of 2 commonly used dosing regimens to racing fit Thoroughbreds, which will allow jurisdictions to establish withdrawal times in order to prevent inadvertent positive regulatory findings.
authors.affiliation: Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, USA; K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, USA.
authors.forename: H K
authors.initials: HK
authors.lastname: Knych
authors.forename: M M
authors.initials: MM
authors.lastname: Mitchell
authors.forename: S J
authors.initials: SJ
authors.lastname: Steinmetz
authors.forename: D S
authors.initials: DS
authors.lastname: McKemie
mesh_terms: D000318:Adrenergic beta-Agonists / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000652:urine; D000818:Animals; D019540:Area Under Curve; D002976:Clenbuterol / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006736:Horses / Q000502:physiology*; D008297:Male; D010805:Physical Conditioning, Animal / Q000502:physiology*
chemical_list: D000318:Adrenergic beta-Agonists; D002976:Clenbuterol
keywords: beta-2 agonist; clenbuterol; horse; horseracing; pharmacokinetics