CHARACTERIZATION OF A PRIMATE MODEL OF ASTHMA USING ANTI-ALLERGY ANTI-ASTHMA AGENTS/

The following study was performed to further characterize a primate mo del of asthma using classes of drugs that target allergy (pyrilamine, cetirizine), are bronchodilators for the treatment of asthma (salbutam ol, salmeterol) or are anti-inflammatory (dexamethasone). These drugs were examined for their ability to inhibit acute, antigen-induced bron choconstriction, the development of airway hyperresponsiveness (AHR) a nd the infiltration of leukocytes into the lungs of atopic cynomolgus monkeys (Macaca facsicularis) using a 10-day, multiple antigen (Ag) ch allenge protocol. All compounds except dexamethasone and cetirizine si gnificantly (p < 0.05) reduced acute, Ag-induced bronchoconstriction ( salbutamol: 74.2%, salmeterol: 52.6%%, pyrilamine: 62.4% inhibition) c ompared to vehicle control trials. Only dexamethasone and salmeterol p revented the development of AHR to methacholine challenge by 90.4 +/- 6.81% and 85.7 +/- 5.61% respectively. Dexamethasone significantly red uced the Ag-induced increase in BAL eosinophils by 85.9 +/- 8.53%. Cet irizine reduced the eosinophil response in 5 of 6 monkeys and salmeter ol demonstrated a trend towards reduced eosinophil increases after mul tiple AE challenge, but neither of these were statistically significan t. These results further illustrate the utility of this model in predi cting compound effects against several relevant functional endpoints t hat are consistent with the effects of similar classes of compounds in humans.