Effect of prolonged administration of clenbuterol on airway reactivity and sweating in horses with inflammatory airway disease.
OBJECTIVE
To determine whether prolonged administration of clenbuterol results in tachyphylaxis, specifically regarding its bronchoprotective properties and effect on sweating in horses.


METHODS
8 Thoroughbreds with inflammatory airway disease.


METHODS
In a crossover design, horses received clenbuterol (0.8 μg/kg, p.o., q 12 h) or placebo for 21 days, with a washout period of ≥ 30 days between the 2 treatments. Airway reactivity was evaluated by use of flowmetric plethysmography and histamine broncho-provocation before (day 0; baseline) and every 7 days after the start of treatment. Sweat function was evaluated via response to epinephrine administered ID before and every 10 days after the start of treatment.


RESULTS
The concentration of histamine required to increase total airway obstruction by 35% (PC35) was significantly reduced during treatment with clenbuterol (mean change, 11.5 mg/mL), compared with during administration of the placebo (mean change, -1.56 mg/mL), with a peak effect at 14 days. Tachyphylaxis was evident by day 21, with 7 of 8 horses having a PC35 below the baseline value (mean change, -0.48 mg/mL), which returned to baseline values during the washout period. No effect of clenbuterol was seen in sweat response to epinephrine administration.


CONCLUSIONS
Clenbuterol initially reduced airway sensitivity to inhaled histamine, but tachyphylaxis that resulted in increased airway reactivity was evident by day 21. Although no effects on sweating were detected, the technique may not have been sensitive enough to identify subtle changes. Prolonged administration of clenbuterol likely results in a clinically important reduction in its bronchodilatory effects.
Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348, USA.
Jennifer R
JR
Read
Raymond C
RC
Boston
Getu
G
Abraham
Sebastien H
SH
Bauquier
Lawrence R
LR
Soma
Rose D
RD
Nolen-Walston
D000402:Airway Obstruction / Q000139:chemically induced / Q000188:drug therapy / Q000662:veterinary*; D000818:Animals; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002976:Clenbuterol / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006632:Histamine / Q000008:administration & dosage / Q000009:adverse effects*; D006734:Horse Diseases / Q000139:chemically induced / Q000188:drug therapy*; D006736:Horses; D007007:Hypohidrosis / Q000139:chemically induced / Q000662:veterinary*; D010991:Plethysmography / Q000187:drug effects / Q000662:veterinary; D013618:Tachyphylaxis
D001993:Bronchodilator Agents; D006632:Histamine; D002976:Clenbuterol