A primate model for the evaluation of antihistamines.
Studies of the efficacy of antihistamines in treating human upper airway pathology are difficult to design and conduct. In part, this is the result of a lack of objective measures of the nasal response. The purpose of this study was to develop a monkey model for the objective evaluation of antihistamine effectiveness and, using this model, to study the efficacy of cetirizine. Computer-assisted active anterior rhinomanometry was used to assess nasal airway resistance (NAR) before and after a nasal histamine provocation in conscious rhesus monkeys (Macaca mulatta). To establish dose-response relationships for oral antihistamines in monkeys, we measured the suppression of wheal-and-flare reactions by two such agents, oral cetirizine (CET) 0.1 to 1 mg/kg and chlorpheniramine (CHL) 0.07 to 0.2 mg/kg. The decreases in wheal sizes were maximal 60 to 120 minutes after CET 1.0 mg/kg (90%), and after CHL 0.2 mg/kg (70%). The four monkeys were challenged intranasally with increasing histamine doses (0.5, 1, 5, and 10 mg). The NAR was measured 15 minutes after each dose. At least three days later and 90 minutes after oral pretreatment with either CET 1 mg/kg or CHL 0.2 mg/kg, the intranasal challenges were repeated. Postchallenge NAR data are given as the percent increase from the baseline NAR values. The four monkeys studied had coefficients of variation of 13%, 15%, 16%, and 26% respectively for baseline studies. Mean percent increases in NAR +/- standard deviation were 14% +/- 0.4%, 47% +/- 10.0%, 45% +/- 3.0%, and 72% +/- 6.0% after intranasal challenge with 0.5, 1, 5, and 10 mg of histamine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
D000284:Administration, Oral; D000403:Airway Resistance; D000818:Animals; D001985:Bronchial Provocation Tests; D017332:Cetirizine; D002744:Chlorpheniramine / Q000627:therapeutic use*; D004341:Drug Evaluation; D006632:Histamine; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006919:Hydroxyzine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008253:Macaca mulatta; D008365:Manometry; D009666:Nose / Q000503:physiopathology; D006255:Rhinitis, Allergic, Seasonal / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D012882:Skin Tests; D012984:Software
D006634:Histamine H1 Antagonists; D006919:Hydroxyzine; D002744:Chlorpheniramine; D006632:Histamine; D017332:Cetirizine